Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01986881
• Collaborator: Pfizer (Industry)
• Enrollment: 8,246
• Arms: 3
• Actual Duration (Months): 73.7

Study Details

Study Description

Brief Summary

An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled).

Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Ertugliflozin; Drug: Placebo; Drug: Glycemic Rescue	Phase 3

Detailed Description

The primary hypotheses for the 4 studies are:

1. Overall Cardiovascular Study:

The time to first occurrence of the composite endpoint of MACE: cardiovascular death, non-fatal myocardial infarction [MI] or non-fatal stroke in participants treated with ertugliflozin is non-inferior compared to that in participants treated with placebo.

1. The 3 Glycemic Sub-studies:

2. The mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo.

3. The mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8246 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess Cardiovascular Outcomes Following Treatment With Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus and Established Vascular Disease, The VERTIS CV Study
• Actual Study Start Date: Nov 4, 2013
• Actual Primary Completion Date: Dec 27, 2019
• Actual Study Completion Date: Dec 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ertugliflozin, 15 mg Ertugliflozin 15 mg administered orally once daily for up to approximately 6 years	Drug: Ertugliflozin; Oral, once daily, for up to approximately 6 years; Other Names: MK-8835, PF-04971729, Steglatro ; Drug: Glycemic Rescue; Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea [SU], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site.
Experimental: Ertugliflozin, 5 mg Ertugliflozin 5 mg administered orally once daily for up to approximately 6 years	Drug: Ertugliflozin; Oral, once daily, for up to approximately 6 years; Other Names: MK-8835, PF-04971729, Steglatro ; Drug: Placebo; Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years; Drug: Glycemic Rescue; Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea [SU], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site.
Placebo Comparator: Placebo Matching placebo to ertugliflozin administered orally once daily for up to approximately 6 years	Drug: Placebo; Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years; Drug: Glycemic Rescue; Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea [SU], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site.

Outcome Measures

Primary Outcome Measures

1. Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke. The on-treatment approach included confirmed events that occurred between the date of first dose of study medication and the on-treatment censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or 365 days after the last dose).

2. Baseline Hemoglobin A1C (A1C) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline]

   A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.

3. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline and Week 18]

   A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

4. Baseline Hemoglobin A1C (A1C) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Baseline]

   A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.

5. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Baseline and Week 18]

   A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

6. Baseline Hemoglobin A1C (A1C) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Baseline]

   A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects Week 0 A1C.

7. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Baseline and Week 18]

   A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

Secondary Outcome Measures

1. Time to Occurrence of Cardiovascular (CV) Death or Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the occurrence of any of the following adjudicated components of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)) or hospitalization for heart failure. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, or last contact date).

2. Time to Occurrence of Cardiovascular Death (On-study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the occurrence of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to CV death or time to censoring (the earliest of participants' end of study date or date last known to be alive).

3. Time to First Occurrence of the Renal Composite: the Composite of Renal Death, Renal Dialysis/Transplant, or Doubling of Serum Creatinine From Baseline (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Renal composite endpoint was defined as a composite of renal death, renal dialysis/transplant, or doubling of serum creatinine from baseline. The on-study approach included events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

4. Time to First Occurrence of MACE Plus (Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke or Hospitalization for Unstable Angina) (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the first occurrence of any of the following adjudicated components 4-point MACE: cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina pectoris. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

5. Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date).

6. Time to First Occurrence of Fatal or Non-fatal Stroke (FNF Stroke) (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the first occurrence of fatal and no-fatal stroke. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

7. Time to First Occurrence of Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the first occurrence of heart failure requiring hospitalization (adjudicated). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.

8. Time to Occurrence of Death From Any Cause (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   Time to the occurrence of death from any cause. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or date last known to be alive. The on-study approach included events that occurred between the randomization date and the on-study censor date.

9. Andersen-Gill Model for Total MACE (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

   All events (first and recurrent) of the composite of MACE (3-point major adverse cardiovascular events: cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke) were assessed using Andersen-Gill model. The on-study approach included events that occurred between the randomization date and the on-study censor date.

10. Andersen-Gill Model for All Cardiovascular Death (CV Death) or Hospitalizations for Heart Failure (HFF) (On-Study Approach) (Overall Cardiovascular Study) [Up to approximately 6 years]

    All events (first and recurrent) of the composite of CV death and HHF were assessed using an Andersen-Gill model. Person-years were calculated as the sum of time from randomization to end of follow-up. The on-study approach included events that occurred between the randomization date and the on-study censor date.

11. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Overall Cardiovascular Study) [Baseline and Week 18]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

12. Change From Baseline in A1C at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

13. Change From Baseline in A1C at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 24 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

14. Change From Baseline in A1C at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 36 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

15. Change From Baseline in A1C at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 48 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

16. Change From Baseline in A1C at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 60 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

17. Change From Baseline in A1C at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 72 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.

18. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Overall Cardiovascular Study) [Week 18]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

19. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 52 (Overall Cardiovascular Study) [Week 52]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

20. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 24 (Overall Cardiovascular Study) [Month 24]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

21. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 36 (Overall Cardiovascular Study) [Month 36]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

22. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 48 (Overall Cardiovascular Study) [Month 48]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

23. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 60 (Overall Cardiovascular Study) [Month 60]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

24. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 18 (Overall Cardiovascular Study) [Week 18]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

25. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 52 (Overall Cardiovascular Study) [Week 52]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

26. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 24 (Overall Cardiovascular Study) [Month 24]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

27. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 36 (Overall Cardiovascular Study) [Month 36]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

28. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 48 (Overall Cardiovascular Study) [Month 48]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

29. Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 60 (Overall Cardiovascular Study) [Month 60]

    A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.

30. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study) [Baseline and Week 18]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

31. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Week 52 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

32. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 24 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

33. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 36 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

34. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 48 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

35. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 60 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

36. Change From Baseline in Fasting Plasma Glucose (FPG) at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    FPG was analyzed after an overnight fast. This change from baseline reflects the Month 72 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.

37. Time to the First Occurrence of a Participant Receiving Glycemic Rescue Therapy Through Week 18 (Overall Cardiovascular Study) [Up to 18 weeks]

    Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication.

38. Time to Initiation of Insulin for Participants Not on Insulin at Baseline (Overall Cardiovascular Study) [Up to approximately 6 years]

    Participants who were not on insulin therapy at the start of study medication.

39. Baseline Insulin Dose for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline]

    Baseline reflects Week 0 insulin dose.

40. Change From Baseline in Insulin Dose at Week 18 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline and Week 18]

    This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

41. Change From Baseline in Insulin Dose at Week 52 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline and Week 52]

    This change from baseline reflects the Week 52 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

42. Change From Baseline in Insulin Dose at Month 24 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline and Month 24]

    This change from baseline reflects the Month 24 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

43. Change From Baseline in Insulin Dose at Month 36 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline and Month 36]

    This change from baseline reflects the Month 36 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

44. Change From Baseline in Insulin Dose at Month 48 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline and Month 48]

    This change from baseline reflects the Month 48 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

45. Change From Baseline in Insulin Dose at Month 60 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study) [Baseline and Month 60]

    This change from baseline reflects the Month 60 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.

46. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study) [Baseline and Week 18]

    This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

47. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    This change from baseline reflects the Week 52 sitting SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

48. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    This change from baseline reflects the Month 24 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

49. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    This change from baseline reflects the Month 36 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

50. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    This change from baseline reflects the Month 48 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

51. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    This change from baseline reflects the Month 60 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

52. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    This change from baseline reflects the Month 72 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

53. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study) [Baseline and Week 18]

    This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

54. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    This change from baseline reflects the Week 52 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

55. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    This change from baseline reflects the Month 24 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

56. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    This change from baseline reflects the Month 36 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

57. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    This change from baseline reflects the Month 48 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

58. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    This change from baseline reflects the Month 60 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

59. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    This change from baseline reflects the Month 72 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.

60. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study) [Baseline and Week 18]

    This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

61. Change From Baseline in Body Weight at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    This change from baseline reflects the Week 52 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

62. Change From Baseline in Body Weight at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    This change from baseline reflects the Month 24 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

63. Change From Baseline in Body Weight at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    This change from baseline reflects the Month 36 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

64. Change From Baseline in Body Weight at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    This change from baseline reflects the Month 48 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

65. Change From Baseline in Body Weight at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    This change from baseline reflects the Month 60 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

66. Change From Baseline in Body Weight at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    This change from baseline reflects the Month 72 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.

67. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 18 (Overall Cardiovascular Study) [Baseline and Week 18]

    This change from baseline reflects the Week 18 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

68. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    This change from baseline reflects the Week 52 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level.

69. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    This change from baseline reflects the Month 24 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

70. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    This change from baseline reflects the Month 36 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

71. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    This change from baseline reflects the Month 48 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level.

72. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    This change from baseline reflects the Month 60 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

73. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    This change from baseline reflects the Month 72 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.

74. Baseline Serum Creatinine (Overall Cardiovascular Study) [Baseline]

    Baseline reflects Week 0 serum creatinine.

75. Change From Baseline in Serum Creatinine at Week 18 (Overall Cardiovascular Study) [Baseline and Week 18]

    This change from baseline reflects the Week 18 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

76. Change From Baseline in Serum Creatinine at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    This change from baseline reflects the Week 52 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

77. Change From Baseline in Serum Creatinine at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    This change from baseline reflects the Month 24 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

78. Change From Baseline in Serum Creatinine at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    This change from baseline reflects the Month 36 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

79. Change From Baseline in Serum Creatinine at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    This change from baseline reflects the Month 48 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

80. Change From Baseline in Serum Creatinine at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    This change from baseline reflects the Month 60 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

81. Change From Baseline in Serum Creatinine at Month 72 (Overall Cardiovascular Study) [Baseline and Month 72]

    This change from baseline reflects the Month 72 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.

82. Baseline Urinary Albumin/Creatinine Ratio (Overall Cardiovascular Study) [Baseline]

    Baseline reflects Week 0 albumin/creatinine ratio.

83. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 18 (Overall Cardiovascular Study) [Baseline and Week 18]

    This percent change relative to baseline reflects the Week 18 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

84. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 52 (Overall Cardiovascular Study) [Baseline and Week 52]

    This percent change relative to baseline reflects the Week 52 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

85. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 24 (Overall Cardiovascular Study) [Baseline and Month 24]

    This percent change relative to baseline reflects the Month 24 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

86. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 36 (Overall Cardiovascular Study) [Baseline and Month 36]

    This percent change relative to baseline reflects the Month 36 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

87. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 48 (Overall Cardiovascular Study) [Baseline and Month 48]

    This percent change relative to baseline reflects the Month 48 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

88. Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 60 (Overall Cardiovascular Study) [Baseline and Month 60]

    This percent change relative to baseline reflects the Month 60 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.

89. Percentage of Participants With Albuminuria Progression or Regression at Week 18 (Overall Cardiovascular Study) [Week 18]

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal-albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

90. Percentage of Participants With Albuminuria Progression or Regression at Week 52 (Overall Cardiovascular Study) [Week 52]

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

91. Percentage of Participants With Albuminuria Progression or Regression at Month 24 (Overall Cardiovascular Study) [Month 24]

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

92. Percentage of Participants With Albuminuria Progression or Regression at Month 36 (Overall Cardiovascular Study) [Month 36]

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

93. Percentage of Participants With Albuminuria Progression or Regression at Month 48 (Overall Cardiovascular Study) [Month 48]

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline and normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

94. Percentage of Participants With Albuminuria Progression or Regression at Month 60 (Overall Cardiovascular Study) [Month 60]

    Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).

95. Percentage of Participants Experiencing an Adverse Event (AE) (Overall Cardiovascular Study) [Up to approximately 6 years]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

96. Percentage of Participants Experiencing an Adverse Event (AE) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Up to 18 weeks]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

97. Percentage of Participants Experiencing an Adverse Event (AE) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Up to 18 weeks]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

98. Percentage of Participants Experiencing an Adverse Event (AE) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Up to 18 weeks]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

99. Percentage of Participants Discontinuing Study Treatment Due to An AE (Overall Cardiovascular Study) [Up to approximately 6 years]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

100. Percentage of Participants Discontinuing Study Treatment Due to An AE (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Up to 18 weeks]

     An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

101. Percentage of Participants Discontinuing Study Treatment Due to An AE (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Up to 18 weeks]

     An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

102. Percentage of Participants Discontinuing Study Treatment Due to An AE (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Up to 18 weeks]

     An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

103. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline and Week 18]

     FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in the FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

104. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

105. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Week 18]

     A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

106. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

107. Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 DBP minus the Week 0 BBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

108. Baseline Insulin Dose for Participants Receiving Insulin at Baseline - (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline]

     Baseline reflects Week 0 insulin dose.

109. Change From Baseline at Week 18 in Insulin Dose for Participants Receiving Insulin at Baseline - Including Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a decrease in insulin dose. Participants who met glycemic rescue criteria received glycemic rescue medication. "Including rescue", included data following the initiation of rescue therapy.

110. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Baseline and Week 18]

     FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

111. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

112. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Week 18]

     A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

113. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

114. Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

115. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Baseline and Week 18]

     FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

116. Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

117. Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Week 18]

     A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

118. Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

119. Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study) [Baseline and Week 18]

     This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria (Overall Cardiovascular Study):

• Diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines

• Hemoglobin A1c (A1C) at the start of study participation of 7.0-10.5% (53-91 mmol/mol)

• On stable allowable anti-hyperglycemic agents (AHA) or on no background AHA for at least 8 weeks prior to the study participation

• Body Mass Index (BMI) > or = to 18.0 kg/m^2

• Evidence or a history of atherosclerosis involving the coronary, cerebral or peripheral vascular systems

• There is adequate documentation of the objective evidence that the participant has established vascular disease such as investigational site's medical records, copies of such records from other institutions, or a letter from a referring physician that specifically states the diagnosis and date of the most recent occurrence of the qualifying event(s) or procedure(s).

• Male, female not or reproductive potential, or female of reproductive potential who agrees to be abstinent from heterosexual activity or agrees to use or have their partner use 2 acceptable methods of contraception

Exclusion Criteria (Overall Cardiovascular Study):

• Previous randomization into this trial

• Experiencing a cardiovascular event (myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening Visit and randomization

• Undergoing any cardiovascular surgery (valvular surgery) within 3 months of study participation

• Planned revascularization or peripheral intervention procedure or other cardiovascular surgery

• New York Heart Association (NYHA) IV heart failure at study participation

• History of type 1 diabetes mellitus or a history of ketoacidosis

Key Inclusion Criteria for the 3 Glycemic Sub-studies:

1. Insulin With or Without Metformin Sub-study: Stable doses of insulin (>=20 units/day, with variations up to 10% in the daily dose permitted) with or without metformin (>=1500 mg/day) for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.

2. Sulfonylurea (SU) Monotherapy Sub-study: Participants receiving a stable dose of SU monotherapy for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.

3. Metformin with SU Sub-study: Participants receiving a stable dose metformin (≥1500 mg/day) with a SU for at least 8 weeks prior to the time of the Screening Visit (V1) and during the period between the Screening Visit (V1) and randomization.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC
• Pfizer

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol - Mar 11, 2016
• Statistical Analysis Plan - Mar 20, 2020

More Information

Publications

• Cannon CP, McGuire DK, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Charbonnel B, Shih WJ, Gallo S, Masiukiewicz U, Golm G, Cosentino F, Lauring B, Terra SG; VERTIS-CV Investigators. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J. 2018 Dec;206:11-23. doi: 10.1016/j.ahj.2018.08.016. Epub 2018 Sep 5.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01986881
• Other Study ID Numbers: 8835-004; 2013-002518-11; B1521021
• First Posted: Nov 19, 2013
• Last Update Posted: Feb 15, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Vascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Ertugliflozin

Study Results

Participant Flow

Recruitment Details	This study included participants in 34 countries at 548 study centers (Overall Cardiovascular Study).

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Period Title: Overall Study
STARTED	2752	2747	2747
Treated	2746	2747	2745
Participants Enrolled in the Insulin +/- Metformin Glycemic Sub-Study	348	370	347
Participants Enrolled in the Sulfonylurea Monotherapy Glycemic Sub-Study	55	54	48
Participants Enrolled in the Metformin With Sulfonylurea Glycemic Sub-Study	100	113	117
COMPLETED	2422	2401	2389
NOT COMPLETED	330	346	358

Baseline Characteristics

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	Total
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Total of all reporting groups
Overall Participants	2752	2747	2747	8246
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.3 (8.2)	64.4 (8.0)	64.4 (8.0)	64.4 (8.1)
Sex: Female, Male (Count of Participants)
Female	801 29.1%	832 30.3%	844 30.7%	2477 30%
Male	1951 70.9%	1915 69.7%	1903 69.3%	5769 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	353 12.8%	347 12.6%	343 12.5%	1043 12.6%
Not Hispanic or Latino	2390 86.8%	2392 87.1%	2399 87.3%	7181 87.1%
Unknown or Not Reported	9 0.3%	8 0.3%	5 0.2%	22 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	13 0.5%	8 0.3%	17 0.6%	38 0.5%
Asian	187 6.8%	149 5.4%	162 5.9%	498 6%
Native Hawaiian or Other Pacific Islander	4 0.1%	10 0.4%	15 0.5%	29 0.4%
Black or African American	91 3.3%	75 2.7%	69 2.5%	235 2.8%
White	2390 86.8%	2436 88.7%	2414 87.9%	7240 87.8%
More than one race	67 2.4%	69 2.5%	70 2.5%	206 2.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Fasting Plasma Glucose (FPG) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	176.1 (52.5)	174.8 (51.6)	173.6 (49.4)	174.8 (51.2)
Sitting Systolic Blood Pressure (SBP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	133.7 (13.7)	133.2 (13.8)	133.1 (13.9)	133.3 (13.8)
Sitting Diastolic Blood Pressure (DBP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	76.8 (8.5)	76.7 (8.2)	76.4 (8.7)	76.6 (8.5)
Body Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	91.9 (18.4)	91.6 (18.6)	91.9 (18.3)	91.8 (18.4)
Hemoglobin A1C (A1C) (A1C Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [A1C Percentage]	8.3 (1.0)	8.2 (1.0)	8.2 (0.9)	8.2 (1.0)
Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73 m^2]	76.0 (20.8)	76.2 (20.9)	75.7 (20.8)	76.0 (20.9)

Outcome Measures

1. Primary Outcome

Title	Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study)
Description	Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke. The on-treatment approach included confirmed events that occurred between the date of first dose of study medication and the on-treatment censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or 365 days after the last dose).
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized into the study and who received at least 1 dose of study medication.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745	5493
Number [Events per 100 Person-years]	3.64	4.16	4.01	3.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	1-sided p-value and the non-inferiority margin is a hazard ratio of 1.3.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox Proportional Hazards Model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95.6%; 0.848 to 1.114
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	1-sided p-value and the non-inferiority margin is a hazard ratio of 1.3.
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95.6%; 0.887 to 1.211
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	1-sided p-value and the non-inferiority margin is a hazard ratio of 1.3.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95.6%; 0.773 to 1.065
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Baseline Hemoglobin A1C (A1C) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, and had a measurement of the analysis endpoint at Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Ins+/-Met Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Mean (Standard Deviation) [A1C Percentage]	8.45 (0.944)	8.38 (0.985)	8.39 (0.928)

3. Primary Outcome

Title	Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least 1 dose of study medication, and had at least 1 measurement of the analysis endpoint for the specified timepoint(s) from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Ins+/-Met Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.77	-0.84	-0.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR, stratum, and the interaction of time by treatment. The stratum was (insulin alone or insulin+metformin) and "Time" was a categorical variable.
	Method	cLDA Model
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -0.78 to -0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR, stratum, and the interaction of time by treatment. The stratum was (insulin alone or insulin+metformin) and "Time" was a categorical variable.
	Method	Constrained longitudinal data analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -0.71 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Baseline Hemoglobin A1C (A1C) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonyl Monotherapy Glycemic Sub-study, and had a measurement of the analysis endpoint at Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	54	54	48
Mean (Standard Deviation) [A1C Percentage]	8.27 (0.999)	8.39 (1.019)	8.21 (1.169)

5. Primary Outcome

Title	Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonyl Monotherapy Glycemic Sub-study, received at least 1 dose of study medication, and had at least 1 measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.91	-0.78	-0.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.247
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR, and the interaction of time by treatment.
	Method	cLDA Model
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR, and the interaction of time by treatment.
	Method	cLDA model
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.72 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Baseline Hemoglobin A1C (A1C) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects Week 0 A1C.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, and had an assessment for the analysis endpoint at Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	99	113	116
Mean (Standard Deviation) [A1C Percentage]	8.39 (0.960)	8.30 (0.963)	8.27 (0.994)

7. Primary Outcome

Title	Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, received at least one dose of blinded study medication, and had at least one assessment for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.89	-0.98	-0.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR, and the interaction of time by treatment.
	Method	cLDA Model
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95%; -0.98 to -0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR, and the interaction of time by treatment.
	Method	cLDA model
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -0.89 to -0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Time to Occurrence of Cardiovascular (CV) Death or Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)
Description	Time to the occurrence of any of the following adjudicated components of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)) or hospitalization for heart failure. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, or last contact date).
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	2.36	2.33	2.66	2.34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95.8%; 0.750 to 1.034
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.150
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95.8%; 0.725 to 1.057
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.188
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95.8%; 0.735 to 1.068
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Time to Occurrence of Cardiovascular Death (On-study Approach) (Overall Cardiovascular Study)
Description	Time to the occurrence of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to CV death or time to censoring (the earliest of participants' end of study date or date last known to be alive).
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	1.77	1.74	1.90	1.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.385
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95.8%; 0.767 to 1.113
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.417
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95.8%; 0.739 to 1.139
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.494
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95.8%; 0.750 to 1.154
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Time to First Occurrence of the Renal Composite: the Composite of Renal Death, Renal Dialysis/Transplant, or Doubling of Serum Creatinine From Baseline (On-Study Approach) (Overall Cardiovascular Study)
Description	Renal composite endpoint was defined as a composite of renal death, renal dialysis/transplant, or doubling of serum creatinine from baseline. The on-study approach included events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	0.87	0.98	1.15	0.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.081
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95.8%; 0.630 to 1.036
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments
	Method	Cox Proportional Hazard Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor. Renal
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95.8%; 0.638 to 1.137
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.065
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95.8%; 0.568 to 1.028
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Time to First Occurrence of MACE Plus (Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke or Hospitalization for Unstable Angina) (On-Study Approach) (Overall Cardiovascular Study)
Description	Time to the first occurrence of any of the following adjudicated components 4-point MACE: cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina pectoris. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	4.42	4.67	4.92	4.54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.183
	Comments	Hazard ratio, CI, and 2-sided p-value comparing All Ertugliflozin versus Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.823 to 1.038
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.450
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.831 to 1.086
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.123
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.785 to 1.029
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction (On-Study Approach) (Overall Cardiovascular Study)
Description	Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date).
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	1.55	2.00	1.70	1.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.676
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.861 to 1.259
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.139
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.949 to 1.451
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.416
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.727 to 1.141
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Time to First Occurrence of Fatal or Non-fatal Stroke (FNF Stroke) (On-Study Approach) (Overall Cardiovascular Study)
Description	Time to the first occurrence of fatal and no-fatal stroke. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	0.92	1.04	0.93	0.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.663
	Comments	Hazard ratio, CI, and 2-sided p-value comparing All Ertugliflozin versus Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.820 to 1.365
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio, CI, and 2-sided p-value comparing All Ertugliflozin versus Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Hazard ratio, confidence interval, and two-sided p-value comparing Ertugliflozin vs Placebo, based on the stratified Cox proportional hazards model that includes treatment as an explanatory factor and cohort category as a stratification factor.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.415
	Comments	A two-sided p-value compared Ertugliflozin vs Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.845 to 1.505
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Hazard ratio, confidence interval, and two-sided p-value comparing Ertugliflozin vs Placebo, based on the stratified Cox proportional hazards model that includes treatment as an explanatory factor and cohort category as a stratification factor.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.953
	Comments	A two-sided p-value compared Ertugliflozin vs Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.736 to 1.334
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Time to First Occurrence of Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)
Description	Time to the first occurrence of heart failure requiring hospitalization (adjudicated). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	0.75	0.72	1.05	0.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	Hazard ratio, CI, and 2-sided p-value comparing All Ertugliflozin versus Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.539 to 0.902
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.502 to 0.932
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.524 to 0.964
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Time to Occurrence of Death From Any Cause (On-Study Approach) (Overall Cardiovascular Study)
Description	Time to the occurrence of death from any cause. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or date last known to be alive. The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	2.42	2.46	2.62	2.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments	Hazard ratio, CI, and 2-sided p-value comparing Ertugliflozin vs Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date.
Statistical Test of Hypothesis	p-Value	0.340
	Comments	Hazard ratio, CI, and 2-sided p-value comparing Ertugliflozin vs Placebo, based on the stratified Cox proportional hazards model that included treatment as an explanatory factor and cohort category as a stratification factor.
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.797 to 1.081
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.463
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.784 to 1.117
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.363
	Comments
	Method	Cox Proportional Hazards Model
	Comments	Model included treatment as an explanatory factor and cohort category as a stratification factor.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.771 to 1.100
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Andersen-Gill Model for Total MACE (On-Study Approach) (Overall Cardiovascular Study)
Description	All events (first and recurrent) of the composite of MACE (3-point major adverse cardiovascular events: cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke) were assessed using Andersen-Gill model. The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	4.35	4.91	4.59	4.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments	Ertugliflozin vs Placebo, based on the Andersen-Gill model for the recurrent events at the end of study. The on-study approach includes confirmed events that occurred between the randomization date and the on-study censor date.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.898 to 1.131
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.937 to 1.219
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.828 to 1.085
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Andersen-Gill Model for All Cardiovascular Death (CV Death) or Hospitalizations for Heart Failure (HFF) (On-Study Approach) (Overall Cardiovascular Study)
Description	All events (first and recurrent) of the composite of CV death and HHF were assessed using an Andersen-Gill model. Person-years were calculated as the sum of time from randomization to end of follow-up. The on-study approach included events that occurred between the randomization date and the on-study censor date.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2752	2747	2747	5499
Number [Events per 100 Person-years]	2.92	2.71	3.42	2.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Overall Cardiovascular Study), All Ertugliflozin (Overall Cardiovascular Study)
	Comments	Ertugliflozin vs Placebo, based on the Andersen-Gill model for the recurrent events at the end of study. The on-study approach included confirmed events that occurred between randomization date and the on-study censor date.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.716 to 0.945
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.673 to 0.935
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ertugliflozin vs Placebo, based on the Andersen-Gill model for the recurrent events at the end of study.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.725 to 1.001
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ertugliflozin vs Placebo, based on the Andersen-Gill model for the recurrent events at the end of study.

18. Secondary Outcome

Title	Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one assessment for the analysis endpoint for the specified timepoint(s) at or after baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2745	2747	2742
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.70	-0.72	-0.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA Model
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA model
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline in A1C at Week 52 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one assessment for the analysis endpoint for the specified timepoint(s) at or after baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.69	-0.67	-0.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Constrained Longitudinal Data Analysis
	Comments	Model included fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Constrained Longitudinal Data Analysis
	Comments	Model included fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Change From Baseline in A1C at Month 24 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 24 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one assessment for the specified timepoint(s) at or after baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.48	-0.46	-0.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
	Method	Constrained longitudinal data analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.45 to -0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ertugliflozin vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
	Method	cLDA
	Comments	Ertugliflozin vs. Placebo.
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.46 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Change From Baseline in A1C at Month 36 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 36 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1590	1574	1501
Mean (95% Confidence Interval) [A1C Percentage]	-0.42	-0.38	-0.04

22. Secondary Outcome

Title	Change From Baseline in A1C at Month 48 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 48 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one assessment for specified timepoint(s) at or after baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [A1C Percentage]	-0.22	-0.17	0.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
	Method	cLDA
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.41 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
	Method	cLDA model
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.46 to -0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline in A1C at Month 60 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 60 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	526	527	477
Mean (95% Confidence Interval) [A1C Percentage]	-0.25	-0.28	-0.10

24. Secondary Outcome

Title	Change From Baseline in A1C at Month 72 (Overall Cardiovascular Study)
Description	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 72 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both baseline and Month 72.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	13	12	9
Mean (95% Confidence Interval) [A1C Percentage]	-0.35	-0.13	0.24

25. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2544	2520	2527
Number [Percentage of Participants]	28.4 1%	28.2 1%	15.5 0.6%

26. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 52 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2363	2347	2311
Number [Percentage of Participants]	28.3 1%	29.0 1.1%	17.4 0.6%

27. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 24 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1570	1541	1496
Number [Percentage of Participants]	23.9 0.9%	23.8 0.9%	16.6 0.6%

28. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 36 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1592	1578	1507
Number [Percentage of Participants]	23.1 0.8%	22.7 0.8%	16.9 0.6%

29. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 48 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	876	860	786
Number [Percentage of Participants]	24.9 0.9%	22.7 0.8%	18.2 0.7%

30. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 60 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	526	529	478
Number [Percentage of Participants]	18.6 0.7%	20.0 0.7%	16.5 0.6%

31. Secondary Outcome

Title	Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 18 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2544	2520	2727
Number [Percentage of Participants]	9.0 0.3%	8.8 0.3%	4.7 0.2%

32. Secondary Outcome

Title	Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 52 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2363	2347	2311
Number [Percentage of Participants]	9.4 0.3%	10.9 0.4%	6.1 0.2%

33. Secondary Outcome

Title	Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 24 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1570	1541	1496
Number [Percentage of Participants]	9.2 0.3%	8.6 0.3%	5.8 0.2%

34. Secondary Outcome

Title	Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 36 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1592	1578	1507
Number [Percentage of Participants]	7.9 0.3%	8.0 0.3%	5.8 0.2%

35. Secondary Outcome

Title	Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 48 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	876	860	786
Number [Percentage of Participants]	8.1 0.3%	9.1 0.3%	7.5 0.3%

36. Secondary Outcome

Title	Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 60 (Overall Cardiovascular Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized and treated participants with an A1C measurement for the analysis endpoint for the specified timepoint(s) at Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	526	529	478
Number [Percentage of Participants]	5.3 0.2%	9.5 0.3%	6.5 0.2%

37. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2745	2747	2744
Least Squares Mean (95% Confidence Interval) [mg/dL]	-32.18	-34.64	-17.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	CLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-17.56
	Confidence Interval	(2-Sided) 95%; -19.49 to -15.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-15.10
	Confidence Interval	(2-Sided) 95%; -17.03 to -13.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

38. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Week 52 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2352	2328	2295
Mean (95% Confidence Interval) [mg/dL]	-28.63	-28.97	-8.76

39. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Month 24 (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Month 24 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1562	1536	1487
Mean (95% Confidence Interval) [mg/dL]	-22.09	-24.31	-4.39

40. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Month 36 (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Month 36 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1579	1567	1491
Mean (95% Confidence Interval) [mg/dL]	-19.39	-22.59	-3.63

41. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Month 48 (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Month 48 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	868	861	777
Mean (95% Confidence Interval) [mg/dL]	-15.28	-16.16	3.59

42. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Month 60 (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Month 60 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	520	524	473
Mean (95% Confidence Interval) [mg/dL]	-13.87	-11.15	-4.69

43. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Month 72 (Overall Cardiovascular Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Month 72 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both baseline and Month 72.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	13	12	9
Mean (95% Confidence Interval) [mg/dL]	-2.46	-84.83	14.56

44. Secondary Outcome

Title	Time to the First Occurrence of a Participant Receiving Glycemic Rescue Therapy Through Week 18 (Overall Cardiovascular Study)
Description	Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and received glycemic rescue by Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	141	102	275
Median (Inter-Quartile Range) [Days]	59.0	51.0	74.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments	Log-Rank Test for the comparison to Placebo was based on all data (including for those participants who never had the event).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments	Log-Rank Test for the comparison to Placebo was based on all data (including for those participants who never had the event).

45. Secondary Outcome

Title	Time to Initiation of Insulin for Participants Not on Insulin at Baseline (Overall Cardiovascular Study)
Description	Participants who were not on insulin therapy at the start of study medication.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and were not on insulin therapy at the start of study medication.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1442	1499	1400
Median (Full Range) [Days]	602	650	482

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments	Log-Rank Test for the comparison to Placebo was based on all data (including for those participants who never had the event).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments	Log-Rank Test for the comparison to Placebo was based on all data (including for those participants who never had the event).

46. Secondary Outcome

Title	Baseline Insulin Dose for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	Baseline reflects Week 0 insulin dose.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and were treated with insulin at Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1304	1248	1345
Mean (Standard Deviation) [Units/Day]	63.82 (48.11)	62.15 (44.46)	65.74 (46.34)

47. Secondary Outcome

Title	Change From Baseline in Insulin Dose at Week 18 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, were treated with insulin at Baseline, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1297	1237	1304
Mean (95% Confidence Interval) [Units/Day]	1.05	0.81	3.71

48. Secondary Outcome

Title	Change From Baseline in Insulin Dose at Week 52 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 52 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, were treated with insulin at Baseline, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1103	1067	1130
Mean (95% Confidence Interval) [Units/Day]	0.84	-1.69	5.57

49. Secondary Outcome

Title	Change From Baseline in Insulin Dose at Month 24 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 24 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, were treated with insulin at Baseline, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1004	966	998
Mean (95% Confidence Interval) [Units/Day]	0.45	-1.58	6.16

50. Secondary Outcome

Title	Change From Baseline in Insulin Dose at Month 36 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 36 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, were treated with insulin at Baseline, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	465	464	419
Mean (95% Confidence Interval) [Units/Day]	1.64	-1.92	7.99

51. Secondary Outcome

Title	Change From Baseline in Insulin Dose at Month 48 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 48 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, were treated with insulin at Baseline, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	387	384	326
Mean (95% Confidence Interval) [Units/Day]	2.96	-1.87	7.28

52. Secondary Outcome

Title	Change From Baseline in Insulin Dose at Month 60 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 60 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, were treated with insulin at Baseline, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	45	47	38
Mean (95% Confidence Interval) [Units/Day]	-2.47	-1.77	9.42

53. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2746	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-2.51	-2.75	0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.78
	Confidence Interval	(2-Sided) 95%; -3.45 to -2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.53
	Confidence Interval	(2-Sided) 95%; -3.21 to -1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

54. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 52 sitting SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-1.84	-2.41	0.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Mean
	Estimated Value	-3.15
	Confidence Interval	(2-Sided) 95%; -3.85 to -2.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.58
	Confidence Interval	(2-Sided) 95%; -3.28 to -1.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

55. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 24 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 24 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-1.80	-1.82	0.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.72
	Confidence Interval	(2-Sided) 95%; -3.57 to -1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.70
	Confidence Interval	(2-Sided) 95%; -3.56 to -1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

56. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 36 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 36 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1593	1580	1505
Mean (Standard Deviation) [mmHg]	-1.55 (14.56)	-1.21 (15.05)	0.84 (14.63)

57. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 48 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 48 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-2.07	-2.26	0.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.60
	Confidence Interval	(2-Sided) 95%; -3.68 to -1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.79
	Confidence Interval	(2-Sided) 95%; -3.87 to -1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

58. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 60 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 60 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	525	529	479
Mean (Standard Deviation) [mmHg]	-2.18 (15.39)	-1.87 (15.01)	0.62 (15.85)

59. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 72 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 72 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 72.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	13	12	9
Mean (95% Confidence Interval) [mmHg]	1.28	-3.46	2.72

60. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding rescue", excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2746	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.99	-1.08	-0.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -1.37 to -0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Means Squares
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

61. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 52 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 52 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.97	-0.95	-0.15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.81
	Confidence Interval	(2-Sided) 95%; -1.22 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -1.24 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

62. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 24 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 24 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.94	-0.90	-0.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.19 to -0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.22 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

63. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 36 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 36 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1593	1580	1505
Mean (Standard Deviation) [mmHg]	-1.27 (8.94)	-0.92 (8.89)	-0.22 (9.15)

64. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 48 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 48 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	881	868	789
Mean (95% Confidence Interval) [mmHg]	-1.45	-1.42	-0.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
	Method	Constrained longitudinal data analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.46 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
	Method	Constrained longitudinal data analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-0.81
	Confidence Interval	(2-Sided) 95%; -1.48 to -0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

65. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 60 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 60 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	525	529	479
Mean (Standard Deviation) [mmHg]	-1.82 (8.66)	-1.43 (9.36)	-1.26 (9.38)

66. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 72 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 72 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and time point.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	13	12	9
Mean (95% Confidence Interval) [mmHg]	-2.18	1.86	7.29

67. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and have at least and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2746	2745
Least Squares Mean (95% Confidence Interval) [Kilograms]	-2.03	-2.32	-0.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) 95%; -2.07 to -1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.63
	Confidence Interval	(2-Sided) 95%; -1.78 to -1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

68. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 52 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 52 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2746	2745
Least Squares Mean (95% Confidence Interval) [Kilograms]	-2.46	-2.84	-0.39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.45
	Confidence Interval	(2-Sided) 95%; -2.67 to -2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.07
	Confidence Interval	(2-Sided) 95%; -2.28 to -1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

69. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 24 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 24 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2746	2745
Least Squares Mean (95% Confidence Interval) [Kilograms]	-2.75	-3.17	-0.65

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.53
	Confidence Interval	(2-Sided) 95%; -2.83 to -2.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.11
	Confidence Interval	(2-Sided) 95%; -2.39 to -1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

70. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 36 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 36 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and have at least one measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1595	1578	1506
Mean (95% Confidence Interval) [Kilograms]	-3.03	-3.41	-0.98

71. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 48 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 48 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after baseline).

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2746	2745
Least Squares Mean (95% Confidence Interval) [Kilograms]	-3.39	-3.83	-1.29

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.53
	Confidence Interval	(2-Sided) 95%; -2.97 to -2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.10
	Confidence Interval	(2-Sided) 95%; -2.52 to -1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

72. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 60 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 60 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	526	530	478
Mean (95% Confidence Interval) [Kilograms]	-3.66	-4.58	-1.21

73. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 72 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 72 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 72.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	13	12	9
Mean (95% Confidence Interval) [Kilograms]	-4.18	-7.37	-0.98

74. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 18 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 18 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2671	2667	2661
Least Squares Mean (95% Confidence Interval) [mL/min/1.73 m^2]	-1.22	-1.81	-0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Lease Squares Means
	Estimated Value	-1.78
	Confidence Interval	(2-Sided) 95%; -2.41 to -1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.19
	Confidence Interval	(2-Sided) 95%; -1.82 to -0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

75. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 52 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had for the analysis endpoint for the specified timepoint(s) a Baseline measurement and at least one measurement at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2671	2669	2664
Least Squares Mean (95% Confidence Interval) [mL/min/1.73 m^2]	-0.51	-1.18	-0.30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Lease Squares Means
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95%; -1.58 to -0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.91 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

76. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 24 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 24 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1576	1547	1509
Mean (95% Confidence Interval) [mL/min/1.73 m^2]	-1.48	-2.35	-2.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; -0.59 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.28 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

77. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 36 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 36 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1591	1577	1504
Mean (Standard Deviation) [mL/min/1.73 m^2]	-2.4 (14.0)	-2.3 (13.4)	-3.8 (14.1)

78. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 48 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 48 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had for the analysis endpoint for the specified timepoint(s) a Baseline measurement and at least one assessment at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2671	2669	2665
Least Squares Mean (95% Confidence Interval) [mL/min/1.73 m^2]	-2.75	-2.93	-4.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Lease Squares Means
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 0.31 to 2.66
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 95%; 0.49 to 2.84
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on cLDA model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.

79. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 60 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 60 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	520	529	477
Mean (Standard Deviation) [mL/min/1.73 m^2]	-2.4 (15.4)	-2.9 (14.1)	-6.8 (14.3)

80. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 72 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 72 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and time point.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	12	12	9
Mean (Standard Deviation) [mL/min/1.73 m^2]	3.7 (12.9)	0.2 (12.2)	-1.8 (14.1)

81. Secondary Outcome

Title	Baseline Serum Creatinine (Overall Cardiovascular Study)
Description	Baseline reflects Week 0 serum creatinine.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and had a measurement for the analysis endpoint for the specified timepoint at Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)	All Ertugliflozin (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years	Ertugliflozin 5 mg or 15 mg, administered orally, once daily, for up to approximately 6 years
Measure Participants	2739	2740	2736	5479
Mean (Standard Deviation) [mg/dL]	0.992 (0.278)	0.985 (0.277)	0.991 (0.281)	0.998 (0.278)

82. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Week 18 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 18 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2540	2520	2524
Mean (Standard Deviation) [mg/dL]	0.022 (0.154)	0.032 (0.148)	-0.002 (0.138)

83. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Week 52 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Week 52 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2360	2344	2314
Mean (Standard Deviation) [mg/dL]	0.013 (0.166)	0.023 (0.163)	0.004 (0.156)

84. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Month 24 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 24 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1574	1548	1506
Mean (Standard Deviation) [mg/dL]	0.024 (0.176)	0.035 (0.187)	0.034 (0.197)

85. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Month 36 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 36 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1589	1575	1499
Mean (Standard Deviation) [mg/dL]	0.037 (0.194)	0.035 (0.188)	0.049 (0.194)

86. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Month 48 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 48 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	875	865	787
Mean (Standard Deviation) [mg/dL]	0.032 (0.206)	0.036 (0.196)	0.059 (0.210)

87. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Month 60 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 60 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	518	528	476
Mean (Standard Deviation) [mg/dL]	0.027 (0.202)	0.042 (0.216)	0.098 (0.248)

88. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Month 72 (Overall Cardiovascular Study)
Description	This change from baseline reflects the Month 72 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 72

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 72.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	12	12	9
Mean (Standard Deviation) [mg/dL]	-0.034 (0.176)	0.001 (0.120)	-0.013 (0.162)

89. Secondary Outcome

Title	Baseline Urinary Albumin/Creatinine Ratio (Overall Cardiovascular Study)
Description	Baseline reflects Week 0 albumin/creatinine ratio.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and had a measurement for the analysis endpoint for the specified timepoint at baseline.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2686	2660	2684
Median (Inter-Quartile Range) [mg/g]	18.00	19.00	19.00

90. Secondary Outcome

Title	Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 18 (Overall Cardiovascular Study)
Description	This percent change relative to baseline reflects the Week 18 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2472	2450	2478
Median (Inter-Quartile Range) [Percent Change]	-13.40	-14.71	0.00

91. Secondary Outcome

Title	Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 52 (Overall Cardiovascular Study)
Description	This percent change relative to baseline reflects the Week 52 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2306	2277	2257
Median (Inter-Quartile Range) [Percent Change]	-2.53	-6.82	5.41

92. Secondary Outcome

Title	Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 24 (Overall Cardiovascular Study)
Description	This percent change relative to baseline reflects the Month 24 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2125	2084	2025
Median (Inter-Quartile Range) [Percent Change]	-0.73	1.06	17.14

93. Secondary Outcome

Title	Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 36 (Overall Cardiovascular Study)
Description	This percent change relative to baseline reflects the Month 36 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1933	1915	1841
Median (Inter-Quartile Range) [Percent Change]	13.33	3.33	27.03

94. Secondary Outcome

Title	Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 48 (Overall Cardiovascular Study)
Description	This percent change relative to baseline reflects the Month 48 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	825	835	745
Median (Inter-Quartile Range) [Percent Change]	33.33	21.25	50.00

95. Secondary Outcome

Title	Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 60 (Overall Cardiovascular Study)
Description	This percent change relative to baseline reflects the Month 60 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, and had a measurement for the analysis endpoint for the specified timepoint(s) at both Baseline and Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	780	771	692
Median (Inter-Quartile Range) [Percent Change]	30.99	20.00	48.53

96. Secondary Outcome

Title	Percentage of Participants With Albuminuria Progression or Regression at Week 18 (Overall Cardiovascular Study)
Description	Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal-albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, had a baseline measurement, and at least one measurement for the analysis endpoint for the specified timepoint at Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2472	2450	2478
Percentage of Participants with albuminuria progression	7.6 0.3%	7.7 0.3%	10.8 0.4%
Percentage of Participants with albuminuria regression	14.9 0.5%	14.7 0.5%	10.7 0.4%

97. Secondary Outcome

Title	Percentage of Participants With Albuminuria Progression or Regression at Week 52 (Overall Cardiovascular Study)
Description	Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, had a baseline measurement, and at least one measurement for the analysis endpoint for the specified timepoint at Week 52.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2306	2277	2257
Percentage of Participants with albuminuria progression	9.5 0.3%	10.2 0.4%	12.9 0.5%
Percentage of Participants with albuminuria regression	14.6 0.5%	14.8 0.5%	10.2 0.4%

98. Secondary Outcome

Title	Percentage of Participants With Albuminuria Progression or Regression at Month 24 (Overall Cardiovascular Study)
Description	Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, had a baseline measurement, and at least one measurement for the analysis endpoint for the specified timepoint at Month 24.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2125	2084	2025
Percentage of Participants with albuminuria progression	12.1 0.4%	11.0 0.4%	16.9 0.6%
Percentage of Participants with albuminuria regression	14.3 0.5%	13.8 0.5%	9.9 0.4%

99. Secondary Outcome

Title	Percentage of Participants With Albuminuria Progression or Regression at Month 36 (Overall Cardiovascular Study)
Description	Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, had a baseline measurement, and at least one measurement for the analysis endpoint for the specified timepoint at Month 36.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	1933	1915	1841
Participants with albuminuria progression	14.6 0.5%	12.5 0.5%	18.1 0.7%
Participants with albuminuria regression	13.8 0.5%	14.3 0.5%	11.0 0.4%

100. Secondary Outcome

Title	Percentage of Participants With Albuminuria Progression or Regression at Month 48 (Overall Cardiovascular Study)
Description	Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline and normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, had a baseline measurement, and at least one measurement for the analysis endpoint for the specified timepoint at Month 48.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	825	835	745
Percentage of Participants with albuminuria progression	19.5 0.7%	14.9 0.5%	21.5 0.8%
Percentage of Participants with albuminuria regression	11.6 0.4%	12.2 0.4%	9.9 0.4%

101. Secondary Outcome

Title	Percentage of Participants With Albuminuria Progression or Regression at Month 60 (Overall Cardiovascular Study)
Description	Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g).
Time Frame	Month 60

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, received at least one dose of blinded study medication, had a baseline measurement, and at least one measurement for the analysis endpoint for the specified timepoint at Month 60.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	780	771	692
Percentage of Participants with albuminuria progression	18.6 0.7%	14.7 0.5%	22.1 0.8%
Percentage of Participants with albuminuria regression	11.3 0.4%	14.8 0.5%	10.5 0.4%

102. Secondary Outcome

Title	Percentage of Participants Experiencing an Adverse Event (AE) (Overall Cardiovascular Study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Number [Percentage of Participants]	85.8 3.1%	84.6 3.1%	85.6 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -2.8 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen & Nurminen method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -1.6 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen & Nurminen method

103. Secondary Outcome

Title	Percentage of Participants Experiencing an Adverse Event (AE) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Number [Percentage of Participants]	59.2 2.2%	62.4 2.3%	61.1 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -5.8 to 8.4
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen & Nurminen method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -9.2 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen & Nurminen method

104. Secondary Outcome

Title	Percentage of Participants Experiencing an Adverse Event (AE) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Number [Percentage of Participants]	47.3 1.7%	25.9 0.9%	45.8 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -17.7 to 20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen and Nurminen method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	-19.9
	Confidence Interval	(2-Sided) 95%; -37.5 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen and Nurminen method

105. Secondary Outcome

Title	Percentage of Participants Experiencing an Adverse Event (AE) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Number [Percentage of Participants]	48.0 1.7%	54.9 2%	47.0 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	7.9
	Confidence Interval	(2-Sided) 95%; -5.1 to 20.5
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on Miettinen and Nurminen method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -12.3 to 14.2
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen and Nurminen method

106. Secondary Outcome

Title	Percentage of Participants Discontinuing Study Treatment Due to An AE (Overall Cardiovascular Study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)	Ertugliflozin 15 mg (Overall Cardiovascular Study)	Placebo (Overall Cardiovascular Study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years	Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years	Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years
Measure Participants	2746	2747	2745
Number [Percentage of Participants]	7.5 0.3%	7.3 0.3%	6.8 0.2%

107. Secondary Outcome

Title	Percentage of Participants Discontinuing Study Treatment Due to An AE (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Number [Percentage of Participants]	2.9 0.1%	3.8 0.1%	3.7 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.9 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen & Nurminen method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -4.0 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Miettinen & Nurminen method

108. Secondary Outcome

Title	Percentage of Participants Discontinuing Study Treatment Due to An AE (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Number [Percentage of Participants]	3.6 0.1%	1.9 0.1%	2.1 0.1%

109. Secondary Outcome

Title	Percentage of Participants Discontinuing Study Treatment Due to An AE (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, and who received at least one dose of blinded study medication.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Number [Percentage of Participants]	0 0%	2.7 0.1%	1.7 0.1%

110. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in the FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least one dose of blinded study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Least Squares Mean (95% Confidence Interval) [mg/dL]	-26.98	-33.15	-7.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	CLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-25.40
	Confidence Interval	(2-Sided) 95%; -32.84 to -17.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-19.24
	Confidence Interval	(2-Sided) 95%; -26.80 to -11.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

111. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Least Squares Mean (95% Confidence Interval) [Kilograms]	-1.87	-2.13	-0.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.88
	Confidence Interval	(2-Sided) 95%; -2.37 to -1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA model
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.62
	Confidence Interval	(2-Sided) 95%; -2.12 to -1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

112. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Number [Percentage of Participants]	20.7 0.8%	21.1 0.8%	10.7 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Missing data imputed using the Constrained Longitudinal Data Analysis (cLDA) model fitted with fixed effects as in the primary analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Model fitted with fixed effects for treatment, stratum for insulin sub-study, covariates for baseline A1C and baseline eGFR (continuous).
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio Relative to Placebo
	Estimated Value	2.49
	Confidence Interval	(2-Sided) 95%; 1.61 to 3.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Missing data imputed using the Constrained Longitudinal Data Analysis (cLDA) model fitted with fixed effects as in the primary analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Model fitted with fixed effects for treatment, stratum for insulin sub-study, covariates for baseline A1C and baseline eGFR (continuous).
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio Relative to Placebo
	Estimated Value	2.60
	Confidence Interval	(2-Sided) 95%; 1.64 to 4.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

113. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least one dose of study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Least Squares Mean (95% Confidence Interval) [mmHg]	-2.67	-2.12	0.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.32
	Confidence Interval	(2-Sided) 95%; -4.35 to -0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-2.88
	Confidence Interval	(2-Sided) 95%; -4.94 to -0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

114. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 DBP minus the Week 0 BBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least one dose of study medication, and had at least one measurement for the analysis endpoint for the specified timepoint(s) at or after Baseline.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.86	-0.64	-0.26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.533
	Comments
	Method	cLDA model
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -1.56 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.326
	Comments
	Method	cLDA model
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -1.81 to 0.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

115. Secondary Outcome

Title	Baseline Insulin Dose for Participants Receiving Insulin at Baseline - (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	Baseline reflects Week 0 insulin dose.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, and received insulin at baseline.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	348	370	347
Mean (Standard Deviation) [Unit/day]	70.76 (44.15)	67.29 (41.23)	73.20 (49.58)

116. Secondary Outcome

Title	Change From Baseline at Week 18 in Insulin Dose for Participants Receiving Insulin at Baseline - Including Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a decrease in insulin dose. Participants who met glycemic rescue criteria received glycemic rescue medication. "Including rescue", included data following the initiation of rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Insulin +/- Metformin Glycemic Sub-study, received at least one dose of study medication and had measurements of the analysis endpoint for the specified timepoint(s) both at Baseline and Week 18, and received insulin at baseline.

Arm/Group Title	Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	Placebo (Insulin +/- Metformin Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	347	366	346
Mean (Standard Deviation) [Unit/day]	-0.71 (10.14)	-2.14 (10.23)	-0.29 (11.49)

117. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Least Squares Mean (95% Confidence Interval) [mg/dL]	-28.28	-26.97	-14.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-12.22
	Confidence Interval	(2-Sided) 95%; -27.03 to 2.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-13.53
	Confidence Interval	(2-Sided) 95%; -28.06 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

118. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Least Squares Mean (95% Confidence Interval) [Kilograms]	-1.75	-1.20	-0.68

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.418
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.79 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments
	Method	cLDA model
	Comments	Model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.07
	Confidence Interval	(2-Sided) 95%; -2.32 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

119. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Number [Percentage of Participants]	32.7 1.2%	27.8 1%	25.0 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Missing data imputed using the Constrained Longitudinal Data Analysis (cLDA) model fitted with fixed effects as in the primary analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.460
	Comments
	Method	Regression, Logistic
	Comments	Model fitted with fixed effects for treatment, covariates for baseline A1C and baseline eGFR (continuous).
Method of Estimation	Estimation Parameter	Odds ratio relative to placebo
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 0.52 to 4.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Missing data imputed using the Constrained Longitudinal Data Analysis (cLDA) model fitted with fixed effects as in the primary analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.335
	Comments
	Method	Regression, Logistic
	Comments	Model fitted with fixed effects for treatment, covariates for baseline A1C and baseline eGFR (continuous).
Method of Estimation	Estimation Parameter	Odds ratio relative to placebo
	Estimated Value	1.62
	Confidence Interval	(2-Sided) 95%; 0.61 to 4.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

120. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.72	-0.80	-3.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.255
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	2.73
	Confidence Interval	(2-Sided) 95%; -2.00 to 7.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.235
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	2.81
	Confidence Interval	(2-Sided) 95%; -1.85 to 7.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

121. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)
Description	This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Sulfonylurea Monotherapy Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	55	54	48
Least Squares Mean (95% Confidence Interval) [mmHg]	-1.18	-0.93	-2.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.178
	Comments
	Method	cLDA model
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	1.98
	Confidence Interval	(2-Sided) 95%; -0.91 to 4.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.230
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR, stratum (insulin alone or insulin + metformin), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	1.73
	Confidence Interval	(2-Sided) 95%; -1.11 to 4.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

122. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Least Squares Mean (95% Confidence Interval) [mg/dL]	-35.28	-36.18	-4.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	CLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-31.37
	Confidence Interval	(2-Sided) 95%; -40.68 to -22.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	cLDA model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-30.47
	Confidence Interval	(2-Sided) 95%; -40.23 to -20.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

123. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Least Squares Mean (95% Confidence Interval) [Kilograms]	-2.04	-2.41	-0.47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) 95%; -2.65 to -1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR (continuous), and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.57
	Confidence Interval	(2-Sided) 95%; -2.30 to -0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

124. Secondary Outcome

Title	Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Number [Percentage of Participants]	37.0 1.3%	32.7 1.2%	12.8 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Missing data imputed using the cLDA model fitted with fixed effects as in the primary analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Model fitted with fixed effects for treatment, covariates for baseline A1C and baseline eGFR (continuous).
Method of Estimation	Estimation Parameter	Adjusted odds ratio relative to placebo
	Estimated Value	4.10
	Confidence Interval	(2-Sided) 95%; 2.00 to 8.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments	Missing data imputed using the cLDA model fitted with fixed effects as in the primary analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Model fitted with fixed effects for treatment, covariates for baseline A1C and baseline eGFR (continuous).
Method of Estimation	Estimation Parameter	Adjusted odds ratio relative to placebo
	Estimated Value	5.97
	Confidence Interval	(2-Sided) 95%; 2.86 to 12.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

125. Secondary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Least Squares Mean (95% Confidence Interval) [mmHg]	-2.26	-1.54	-0.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.597
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -4.00 to 2.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.351
	Comments
	Method	cLDA
	Comments	The model had fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-1.57
	Confidence Interval	(2-Sided) 95%; -4.87 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

126. Secondary Outcome

Title	Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)
Description	This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who were randomized, participated in the Metformin with Sulfonylurea Glycemic Sub-study, received at least one dose of study medication and had at least one measurement of the analysis endpoint for the specified timepoint(s) at any time from Baseline to Week 18.

Arm/Group Title	Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks	Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks	Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
Measure Participants	100	113	117
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.30	-0.92	-0.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 15 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.490
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95%; -2.60 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ertugliflozin 5 mg (Overall Cardiovascular Study), Placebo (Overall Cardiovascular Study)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.958
	Comments
	Method	cLDA
	Comments	Model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -2.07 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Overall Cardiovascular study - Up to approximately 6 years 3 Glycemic Sub-studies - Up to 18 weeks
Adverse Event Reporting Description	The analysis population for all-cause mortality was all randomized participants and the analysis population for adverse events was all participants who received at least one dose of blinded study medication. The Overall Cardiovascular Study had a follow-up of approximately 6 years whereas the glycemic sub-studies had an 18-week follow-up time.
Arm/Group Title	Ertugliflozin 5 mg (Overall Cardiovascular Study)		Ertugliflozin 15 mg (Overall Cardiovascular Study)		Placebo (Overall Cardiovascular Study)		Ertugliflozin 5 mg (Insulin +/- Metformin Sub-study)		Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)		Placebo (Insulin +/- Metformin Glycemic Sub-study)		Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
Arm/Group Description	Ertugliflozin 5 mg, administered orally, once daily, for up to approximately 6 years		Ertugliflozin 15 mg, administered orally, once daily, for up to approximately 6 years		Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years		Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks		Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks		Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks		Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks		Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks		Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks		Ertugliflozin 5 mg, administered orally, once daily, for up to 18 weeks		Ertugliflozin 15 mg, administered orally, once daily, for up to 18 weeks		Matching placebo to ertugliflozin administered orally, once daily, for up to 18 weeks
All Cause Mortality
	Ertugliflozin 5 mg (Overall Cardiovascular Study)		Ertugliflozin 15 mg (Overall Cardiovascular Study)		Placebo (Overall Cardiovascular Study)		Ertugliflozin 5 mg (Insulin +/- Metformin Sub-study)		Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)		Placebo (Insulin +/- Metformin Glycemic Sub-study)		Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	228/2746 (8.3%)		233/2747 (8.5%)		247/2745 (9%)		4/348 (1.1%)		6/370 (1.6%)		1/347 (0.3%)		0/55 (0%)		1/54 (1.9%)		0/48 (0%)		0/100 (0%)		1/113 (0.9%)		0/117 (0%)
Serious Adverse Events
	Ertugliflozin 5 mg (Overall Cardiovascular Study)		Ertugliflozin 15 mg (Overall Cardiovascular Study)		Placebo (Overall Cardiovascular Study)		Ertugliflozin 5 mg (Insulin +/- Metformin Sub-study)		Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)		Placebo (Insulin +/- Metformin Glycemic Sub-study)		Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	958/2746 (34.9%)		937/2747 (34.1%)		990/2745 (36.1%)		33/348 (9.5%)		27/370 (7.3%)		37/347 (10.7%)		4/55 (7.3%)		1/54 (1.9%)		2/48 (4.2%)		7/100 (7%)		8/113 (7.1%)		6/117 (5.1%)
Blood and lymphatic system disorders
Anaemia	5/2746 (0.2%)	5	4/2747 (0.1%)	4	3/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blood loss anaemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemolytic anaemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Immune thrombocytopenic purpura	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Iron deficiency anaemia	1/2746 (0%)	1	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Leukocytosis	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lymphadenopathy	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lymphadenopathy mediastinal	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Microcytic anaemia	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Normocytic anaemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancytopenia	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Polycythaemia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thrombocytopenia	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thrombotic thrombocytopenic purpura	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac disorders
Acute coronary syndrome	9/2746 (0.3%)	9	6/2747 (0.2%)	6	8/2745 (0.3%)	8	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	1/55 (1.8%)	1	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Acute left ventricular failure	3/2746 (0.1%)	3	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Acute myocardial infarction	52/2746 (1.9%)	61	76/2747 (2.8%)	83	73/2745 (2.7%)	80	3/348 (0.9%)	80	1/370 (0.3%)	80	1/347 (0.3%)	80	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	1/113 (0.9%)	1	0/117 (0%)	0
Adams-Stokes syndrome	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Angina pectoris	38/2746 (1.4%)	39	42/2747 (1.5%)	48	49/2745 (1.8%)	54	2/348 (0.6%)	54	2/370 (0.5%)	54	3/347 (0.9%)	54	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Angina unstable	74/2746 (2.7%)	92	71/2747 (2.6%)	78	89/2745 (3.2%)	106	3/348 (0.9%)	106	1/370 (0.3%)	106	1/347 (0.3%)	106	0/55 (0%)	0	0/54 (0%)	0	1/48 (2.1%)	1	0/100 (0%)	0	2/113 (1.8%)	2	0/117 (0%)	0
Anginal equivalent	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aortic valve stenosis	4/2746 (0.1%)	4	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arrhythmia	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arrhythmia supraventricular	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arteriosclerosis coronary artery	3/2746 (0.1%)	3	2/2747 (0.1%)	2	3/2745 (0.1%)	3	0/348 (0%)	3	0/370 (0%)	3	1/347 (0.3%)	3	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atrial fibrillation	30/2746 (1.1%)	33	31/2747 (1.1%)	38	37/2745 (1.3%)	40	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	0/117 (0%)	0
Atrial flutter	11/2746 (0.4%)	12	9/2747 (0.3%)	9	9/2745 (0.3%)	11	1/348 (0.3%)	11	0/370 (0%)	11	0/347 (0%)	11	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atrial tachycardia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atrioventricular block	1/2746 (0%)	1	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atrioventricular block complete	3/2746 (0.1%)	3	2/2747 (0.1%)	2	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atrioventricular block first degree	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atrioventricular block second degree	5/2746 (0.2%)	5	5/2747 (0.2%)	5	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bradyarrhythmia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bradycardia	1/2746 (0%)	1	5/2747 (0.2%)	5	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bundle branch block left	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bundle branch block right	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac arrest	7/2746 (0.3%)	7	15/2747 (0.5%)	15	13/2745 (0.5%)	13	0/348 (0%)	13	0/370 (0%)	13	2/347 (0.6%)	13	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac asthma	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac disorder	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac failure	35/2746 (1.3%)	39	34/2747 (1.2%)	36	43/2745 (1.6%)	58	0/348 (0%)	58	0/370 (0%)	58	1/347 (0.3%)	58	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac failure acute	7/2746 (0.3%)	7	7/2747 (0.3%)	7	8/2745 (0.3%)	11	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	1/54 (1.9%)	1	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac failure chronic	16/2746 (0.6%)	20	10/2747 (0.4%)	12	14/2745 (0.5%)	17	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac failure congestive	19/2746 (0.7%)	23	28/2747 (1%)	37	35/2745 (1.3%)	42	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac tamponade	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac ventricular thrombosis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardio-respiratory arrest	4/2746 (0.1%)	4	5/2747 (0.2%)	5	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiogenic shock	3/2746 (0.1%)	3	4/2747 (0.1%)	4	8/2745 (0.3%)	8	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiomyopathy	2/2746 (0.1%)	2	3/2747 (0.1%)	3	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiopulmonary failure	1/2746 (0%)	1	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiovascular disorder	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiovascular insufficiency	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic left ventricular failure	1/2746 (0%)	1	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Conduction disorder	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Coronary artery disease	35/2746 (1.3%)	43	34/2747 (1.2%)	36	38/2745 (1.4%)	42	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Coronary artery insufficiency	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Coronary artery occlusion	2/2746 (0.1%)	2	5/2747 (0.2%)	6	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Coronary artery stenosis	14/2746 (0.5%)	14	20/2747 (0.7%)	22	16/2745 (0.6%)	18	0/348 (0%)	0	2/370 (0.5%)	2	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Coronary ostial stenosis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypertensive cardiomyopathy	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ischaemic cardiomyopathy	1/2746 (0%)	1	4/2747 (0.1%)	4	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Left ventricular dysfunction	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Left ventricular failure	2/2746 (0.1%)	2	4/2747 (0.1%)	4	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Microvascular coronary artery disease	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mitral valve incompetence	2/2746 (0.1%)	2	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mitral valve stenosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myocardial infarction	39/2746 (1.4%)	39	49/2747 (1.8%)	52	37/2745 (1.3%)	41	1/348 (0.3%)	1	0/370 (0%)	0	2/347 (0.6%)	2	0/55 (0%)	0	1/54 (1.9%)	1	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	1/117 (0.9%)	1
Myocardial ischaemia	17/2746 (0.6%)	17	13/2747 (0.5%)	14	18/2745 (0.7%)	21	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nodal arrhythmia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pericardial effusion	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pericarditis	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postinfarction angina	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Silent myocardial infarction	1/2746 (0%)	1	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sinoatrial block	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sinus bradycardia	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sinus node dysfunction	4/2746 (0.1%)	4	3/2747 (0.1%)	3	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stress cardiomyopathy	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Supraventricular tachyarrhythmia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Supraventricular tachycardia	3/2746 (0.1%)	5	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Systolic dysfunction	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Torsade de pointes	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tricuspid valve incompetence	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Trifascicular block	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ventricular arrhythmia	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ventricular extrasystoles	2/2746 (0.1%)	2	3/2747 (0.1%)	3	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ventricular failure	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ventricular fibrillation	3/2746 (0.1%)	3	5/2747 (0.2%)	5	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ventricular tachycardia	2/2746 (0.1%)	2	13/2747 (0.5%)	13	7/2745 (0.3%)	8	0/348 (0%)	0	1/370 (0.3%)	1	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Congenital, familial and genetic disorders
Atrial septal defect	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hydrocele	1/2746 (0%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Phimosis	6/2746 (0.2%)	6	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ear and labyrinth disorders
Acute vestibular syndrome	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Deafness neurosensory	1/2746 (0%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Deafness unilateral	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meniere's disease	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Middle ear inflammation	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vertigo	4/2746 (0.1%)	4	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vertigo positional	2/2746 (0.1%)	2	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vestibular disorder	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Endocrine disorders
Adrenal haematoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Adrenal mass	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Adrenocortical insufficiency acute	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Goitre	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypothyroidism	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thyroid mass	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Eye disorders
Angle closure glaucoma	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blindness unilateral	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cataract	8/2746 (0.3%)	9	13/2747 (0.5%)	17	17/2745 (0.6%)	22	0/348 (0%)	0	1/370 (0.3%)	1	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cataract nuclear	0/2746 (0%)	0	1/2747 (0%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic retinal oedema	2/2746 (0.1%)	2	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic retinopathy	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diplopia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Eyelid ptosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Glaucoma	1/2746 (0%)	1	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Keratitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Macular degeneration	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Macular fibrosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Macular hole	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Macular oedema	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal artery embolism	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal artery occlusion	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal detachment	0/2746 (0%)	0	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal disorder	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal haemorrhage	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal tear	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Retinal vein thrombosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rhegmatogenous retinal detachment	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tractional retinal detachment	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Uveitis	1/2746 (0%)	1	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vitreoretinal traction syndrome	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vitreous adhesions	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vitreous haemorrhage	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abdominal hernia	1/2746 (0%)	1	3/2747 (0.1%)	3	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abdominal pain	5/2746 (0.2%)	5	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abdominal pain upper	1/2746 (0%)	1	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abdominal wall haematoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Anal fissure	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Anal fistula	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Anal incontinence	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Anogenital dysplasia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ascites	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Buccal polyp	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic gastritis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colitis	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colitis ischaemic	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Constipation	0/2746 (0%)	0	5/2747 (0.2%)	5	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Diabetic gastroparesis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diarrhoea	3/2746 (0.1%)	3	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diverticulum	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	0/117 (0%)	0
Diverticulum intestinal	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diverticulum intestinal haemorrhagic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Duodenal perforation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Duodenal ulcer	2/2746 (0.1%)	2	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Duodenal ulcer haemorrhage	3/2746 (0.1%)	3	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Enterocolitis	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Erosive duodenitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Erosive oesophagitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastric haemorrhage	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastric ulcer	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastric ulcer haemorrhage	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastric ulcer perforation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastritis	0/2746 (0%)	0	1/2747 (0%)	1	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastritis erosive	4/2746 (0.1%)	4	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastritis haemorrhagic	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrointestinal haemorrhage	6/2746 (0.2%)	6	6/2747 (0.2%)	6	6/2745 (0.2%)	7	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrointestinal obstruction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrooesophageal reflux disease	1/2746 (0%)	1	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Haematemesis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haematochezia	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemorrhoidal haemorrhage	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemorrhoids	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ileus	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ileus paralytic	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Incarcerated inguinal hernia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Inguinal hernia	4/2746 (0.1%)	5	5/2747 (0.2%)	5	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal haemorrhage	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal ischaemia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal mass	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal obstruction	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal perforation	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal stenosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Irritable bowel syndrome	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large intestinal haemorrhage	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large intestinal obstruction	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large intestinal stenosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large intestinal ulcer	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large intestine perforation	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large intestine polyp	2/2746 (0.1%)	2	4/2747 (0.1%)	4	3/2745 (0.1%)	4	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lower gastrointestinal haemorrhage	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Melaena	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mesenteric panniculitis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nausea	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Obstructive pancreatitis	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oedematous pancreatitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oesophageal achalasia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oesophageal ulcer	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oesophagitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatic cyst	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatic duct dilatation	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatitis	4/2746 (0.1%)	4	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatitis acute	6/2746 (0.2%)	7	7/2747 (0.3%)	7	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatitis chronic	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatitis haemorrhagic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peptic ulcer	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peptic ulcer haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Proctitis haemorrhagic	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rectal haemorrhage	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rectal polyp	1/2746 (0%)	1	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Salivary gland calculus	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Small intestinal obstruction	0/2746 (0%)	0	2/2747 (0.1%)	2	2/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Small intestinal perforation	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Strangulated umbilical hernia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Subileus	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Umbilical hernia	1/2746 (0%)	1	7/2747 (0.3%)	7	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Upper gastrointestinal haemorrhage	2/2746 (0.1%)	2	6/2747 (0.2%)	6	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vomiting	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
General disorders
Accidental death	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Asthenia	1/2746 (0%)	1	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Catheter site haemorrhage	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Catheter site phlebitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chest discomfort	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chest pain	17/2746 (0.6%)	19	8/2747 (0.3%)	9	8/2745 (0.3%)	8	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Death	35/2746 (1.3%)	35	22/2747 (0.8%)	22	25/2745 (0.9%)	25	3/348 (0.9%)	3	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Fatigue	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hanging	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Inflammation	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Multiple organ dysfunction syndrome	4/2746 (0.1%)	4	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Non-cardiac chest pain	26/2746 (0.9%)	29	16/2747 (0.6%)	18	22/2745 (0.8%)	23	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Physical deconditioning	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Polyp	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pyrexia	3/2746 (0.1%)	4	1/2747 (0%)	1	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stent-graft endoleak	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sudden cardiac death	4/2746 (0.1%)	4	3/2747 (0.1%)	3	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sudden death	2/2746 (0.1%)	2	0/2747 (0%)	0	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ulcer	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular stent occlusion	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular stent stenosis	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatobiliary disorders
Autoimmune hepatitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bile duct obstruction	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bile duct stenosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bile duct stone	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Biliary colic	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Biliary dilatation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholangitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholangitis chronic	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholecystitis	2/2746 (0.1%)	2	7/2747 (0.3%)	7	6/2745 (0.2%)	6	0/348 (0%)	0	2/370 (0.5%)	2	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholecystitis acute	11/2746 (0.4%)	11	4/2747 (0.1%)	4	11/2745 (0.4%)	11	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholecystitis chronic	1/2746 (0%)	1	3/2747 (0.1%)	3	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholelithiasis	5/2746 (0.2%)	5	9/2747 (0.3%)	9	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholelithiasis obstructive	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Drug-induced liver injury	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gallbladder necrosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gallbladder rupture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic cirrhosis	3/2746 (0.1%)	3	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic steatosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatitis acute	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatitis cholestatic	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Jaundice	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Liver injury	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Portal vein thrombosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post cholecystectomy syndrome	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Immune system disorders
Anaphylactic shock	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Drug hypersensitivity	1/2746 (0%)	1	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypersensitivity	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sarcoidosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Infections and infestations
Abdominal abscess	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abdominal wall abscess	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abscess	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abscess jaw	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abscess limb	3/2746 (0.1%)	3	5/2747 (0.2%)	5	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abscess neck	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Abscess of salivary gland	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Actinomycosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Amoebic colitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Amoebic dysentery	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Anal abscess	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Appendicitis	1/2746 (0%)	1	3/2747 (0.1%)	3	3/2745 (0.1%)	3	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arteriosclerotic gangrene	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aspergilloma	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atypical pneumonia	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bacteraemia	0/2746 (0%)	0	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bacterial sepsis	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Beta haemolytic streptococcal infection	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchitis	5/2746 (0.2%)	5	6/2747 (0.2%)	6	11/2745 (0.4%)	11	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchitis bacterial	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchitis viral	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bursitis infective	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Campylobacter gastroenteritis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Carbuncle	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cellulitis	21/2746 (0.8%)	23	31/2747 (1.1%)	33	21/2745 (0.8%)	26	0/348 (0%)	0	3/370 (0.8%)	3	2/347 (0.6%)	2	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholecystitis infective	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic tonsillitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Clostridium difficile colitis	2/2746 (0.1%)	2	1/2747 (0%)	1	2/2745 (0.1%)	2	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colonic abscess	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cystitis	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Device related sepsis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic foot infection	2/2746 (0.1%)	2	1/2747 (0%)	1	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic gangrene	2/2746 (0.1%)	2	4/2747 (0.1%)	6	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diverticulitis	0/2746 (0%)	0	2/2747 (0.1%)	2	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Endocarditis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Endotoxic shock	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Epididymitis	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Erysipelas	2/2746 (0.1%)	2	4/2747 (0.1%)	4	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Escherichia bacteraemia	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Escherichia sepsis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Escherichia urinary tract infection	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Extradural abscess	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gallbladder empyema	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gangrene	16/2746 (0.6%)	18	16/2747 (0.6%)	20	8/2745 (0.3%)	8	0/348 (0%)	0	2/370 (0.5%)	2	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gas gangrene	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastroenteritis	5/2746 (0.2%)	5	4/2747 (0.1%)	4	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastroenteritis bacterial	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastroenteritis clostridial	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastroenteritis norovirus	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastroenteritis rotavirus	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastroenteritis viral	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrointestinal infection	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Graft infection	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Groin abscess	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Groin infection	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haematoma infection	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Helicobacter infection	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatitis C	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Herpes zoster	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Infected skin ulcer	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Infection	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Infective exacerbation of bronchiectasis	1/2746 (0%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Infective thrombosis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Influenza	2/2746 (0.1%)	2	2/2747 (0.1%)	2	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Klebsiella bacteraemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Klebsiella sepsis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Labyrinthitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Laryngitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Liver abscess	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Localised infection	4/2746 (0.1%)	4	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lower respiratory tract infection	1/2746 (0%)	1	2/2747 (0.1%)	2	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lyme disease	1/2746 (0%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lymph node tuberculosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meningitis aseptic	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meningitis viral	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meningoencephalitis bacterial	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metapneumovirus infection	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Muscle abscess	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ophthalmic herpes zoster	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Orchitis	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Osteomyelitis	14/2746 (0.5%)	15	10/2747 (0.4%)	11	6/2745 (0.2%)	8	2/348 (0.6%)	2	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Otitis externa	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paraspinal abscess	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paronychia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Perihepatic abscess	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Periorbital cellulitis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peritonitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peritonsillar abscess	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pharyngeal abscess	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pharyngitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pharyngitis streptococcal	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumococcal sepsis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia	51/2746 (1.9%)	58	46/2747 (1.7%)	48	45/2745 (1.6%)	49	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia bacterial	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia influenzal	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia parainfluenzae viral	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia pseudomonal	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia staphylococcal	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post procedural sepsis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postoperative abscess	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postoperative wound infection	3/2746 (0.1%)	3	4/2747 (0.1%)	4	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pseudomonas infection	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Pulmonary tuberculosis	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pyelonephritis	3/2746 (0.1%)	3	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pyelonephritis acute	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pyelonephritis chronic	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pyoderma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Respiratory syncytial virus infection	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Respiratory tract infection	3/2746 (0.1%)	3	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rhinovirus infection	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Scrotal abscess	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sepsis	22/2746 (0.8%)	23	12/2747 (0.4%)	12	7/2745 (0.3%)	7	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Septic embolus	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Septic encephalopathy	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Septic shock	2/2746 (0.1%)	2	8/2747 (0.3%)	8	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sinusitis	0/2746 (0%)	0	1/2747 (0%)	1	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skin infection	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal cord infection	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Staphylococcal bacteraemia	1/2746 (0%)	1	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Staphylococcal infection	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Staphylococcal sepsis	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Staphylococcal skin infection	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Streptococcal bacteraemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Streptococcal sepsis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Systemic candida	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tonsillitis	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tracheobronchitis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tropical ulcer	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tuberculosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tuberculosis of eye	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Upper respiratory tract infection	2/2746 (0.1%)	2	0/2747 (0%)	0	2/2745 (0.1%)	2	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urinary tract infection	16/2746 (0.6%)	24	10/2747 (0.4%)	10	14/2745 (0.5%)	15	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urinary tract infection bacterial	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urinary tract infection fungal	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urosepsis	2/2746 (0.1%)	2	1/2747 (0%)	1	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vestibular neuronitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Viral infection	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Viral upper respiratory tract infection	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Wound infection	0/2746 (0%)	0	2/2747 (0.1%)	2	3/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Wound infection bacterial	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Wound sepsis	1/2746 (0%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Injury, poisoning and procedural complications
Accident	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Accidental overdose	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Anastomotic leak	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ankle fracture	3/2746 (0.1%)	3	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Arterial bypass occlusion	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arterial bypass stenosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arterial bypass thrombosis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arteriovenous graft site stenosis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Avulsion fracture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Back injury	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain contusion	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac contusion	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cervical vertebral fracture	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Comminuted fracture	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Concussion	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Confusion postoperative	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Contusion	3/2746 (0.1%)	3	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Coronary vascular graft occlusion	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Craniocerebral injury	2/2746 (0.1%)	2	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ear canal injury	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Epiphyseal fracture	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Eye contusion	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Facial bones fracture	2/2746 (0.1%)	3	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Fall	3/2746 (0.1%)	3	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Femoral neck fracture	3/2746 (0.1%)	3	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Femur fracture	6/2746 (0.2%)	6	2/2747 (0.1%)	2	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Fibula fracture	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Foot fracture	1/2746 (0%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Forearm fracture	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Foreign body in respiratory tract	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Fracture displacement	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrointestinal injury	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastrointestinal stoma complication	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hand fracture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Head injury	3/2746 (0.1%)	3	1/2747 (0%)	1	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Heat exhaustion	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hip fracture	4/2746 (0.1%)	4	3/2747 (0.1%)	3	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Humerus fracture	4/2746 (0.1%)	4	2/2747 (0.1%)	2	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Incisional hernia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Injury corneal	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intentional overdose	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Jaw fracture	1/2746 (0%)	3	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Joint dislocation	2/2746 (0.1%)	3	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Joint injury	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ligament sprain	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Limb crushing injury	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Limb injury	4/2746 (0.1%)	4	3/2747 (0.1%)	4	1/2745 (0%)	1	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	0/117 (0%)	0
Limb traumatic amputation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lower limb fracture	0/2746 (0%)	0	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lumbar vertebral fracture	2/2746 (0.1%)	4	1/2747 (0%)	4	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Median nerve injury	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meniscus injury	2/2746 (0.1%)	2	3/2747 (0.1%)	3	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nerve injury	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nerve root injury cervical	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Osteoradionecrosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paranasal sinus injury	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Patella fracture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pelvic fracture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Periprocedural myocardial infarction	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post procedural bile leak	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post procedural discharge	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post procedural haematoma	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post procedural haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Post procedural myocardial infarction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postoperative respiratory failure	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postoperative thoracic procedure complication	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postoperative wound complication	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Postpericardiotomy syndrome	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Procedural nausea	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Procedural pain	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Radius fracture	1/2746 (0%)	1	3/2747 (0.1%)	3	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rib fracture	2/2746 (0.1%)	7	5/2747 (0.2%)	13	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Road traffic accident	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skin laceration	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skull fracture	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skull fractured base	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal compression fracture	1/2746 (0%)	1	5/2747 (0.2%)	5	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal cord injury	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal fracture	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stab wound	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sternal fracture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Subdural haematoma	4/2746 (0.1%)	4	4/2747 (0.1%)	4	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Subdural haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tendon rupture	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thermal burn	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thoracic vertebral fracture	2/2746 (0.1%)	3	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tibia fracture	4/2746 (0.1%)	4	6/2747 (0.2%)	6	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Tooth injury	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Toxicity to various agents	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Traumatic haematoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Traumatic intracranial haemorrhage	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Traumatic lung injury	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ulna fracture	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Upper limb fracture	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular access site haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular injury	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular pseudoaneurysm	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Wound	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Wound dehiscence	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Wound haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Investigations
Anticoagulation drug level above therapeutic	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Antipsychotic drug level increased	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blood creatinine increased	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blood glucose fluctuation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blood glucose increased	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blood pressure increased	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Creatinine renal clearance decreased	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Glomerular filtration rate decreased	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic enzyme increased	3/2746 (0.1%)	3	3/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Liver function test increased	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oxygen saturation decreased	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Transaminases increased	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Troponin T increased	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metabolism and nutrition disorders
Cardiometabolic syndrome	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dehydration	2/2746 (0.1%)	2	3/2747 (0.1%)	3	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetes mellitus	5/2746 (0.2%)	6	1/2747 (0%)	1	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetes mellitus inadequate control	12/2746 (0.4%)	12	6/2747 (0.2%)	7	14/2745 (0.5%)	14	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Diabetic ketoacidosis	4/2746 (0.1%)	5	5/2747 (0.2%)	5	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic metabolic decompensation	4/2746 (0.1%)	6	4/2747 (0.1%)	4	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Fluid overload	1/2746 (0%)	1	0/2747 (0%)	0	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gout	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypercalcaemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hyperglycaemia	3/2746 (0.1%)	4	4/2747 (0.1%)	5	8/2745 (0.3%)	8	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hyperkalaemia	2/2746 (0.1%)	2	4/2747 (0.1%)	4	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hyperosmolar state	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypocalcaemia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypoglycaemia	12/2746 (0.4%)	17	9/2747 (0.3%)	9	14/2745 (0.5%)	14	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hyponatraemia	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypovolaemia	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Insulin-requiring type 2 diabetes mellitus	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ketoacidosis	2/2746 (0.1%)	2	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ketosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lactic acidosis	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metabolic acidosis	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Obesity	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Type 2 diabetes mellitus	0/2746 (0%)	0	2/2747 (0.1%)	4	2/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	4/2746 (0.1%)	4	1/2747 (0%)	1	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arthritis	1/2746 (0%)	1	4/2747 (0.1%)	4	2/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Back pain	4/2746 (0.1%)	4	1/2747 (0%)	1	1/2745 (0%)	1	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bone cyst	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bursitis	0/2746 (0%)	0	1/2747 (0%)	1	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Connective tissue inflammation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Costochondritis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Foot deformity	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gouty arthritis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Groin pain	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemarthrosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intervertebral disc degeneration	1/2746 (0%)	1	1/2747 (0%)	2	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intervertebral disc disorder	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intervertebral disc displacement	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intervertebral disc protrusion	2/2746 (0.1%)	2	3/2747 (0.1%)	3	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Joint contracture	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Joint swelling	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Loose body in joint	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lumbar spinal stenosis	2/2746 (0.1%)	2	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meniscal degeneration	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Muscle fatigue	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Muscle spasms	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Muscular weakness	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Musculoskeletal chest pain	10/2746 (0.4%)	11	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Musculoskeletal pain	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myalgia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myositis	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Osteitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Osteitis deformans	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Osteoarthritis	22/2746 (0.8%)	25	16/2747 (0.6%)	18	21/2745 (0.8%)	23	0/348 (0%)	0	1/370 (0.3%)	1	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Osteochondrosis	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pain in extremity	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Periarthritis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Polyarthritis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Polymyalgia rheumatica	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rhabdomyolysis	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rheumatoid arthritis	3/2746 (0.1%)	3	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rotator cuff syndrome	4/2746 (0.1%)	4	3/2747 (0.1%)	3	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal osteoarthritis	6/2746 (0.2%)	6	3/2747 (0.1%)	3	3/2745 (0.1%)	3	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal pain	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spinal stenosis	1/2746 (0%)	1	2/2747 (0.1%)	2	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spondyloarthropathy	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Spondylolisthesis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Synovial cyst	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Systemic lupus erythematosus	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tenosynovitis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tenosynovitis stenosans	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Undifferentiated connective tissue disease	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Acute myeloid leukaemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Acute promyelocytic leukaemia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Adenocarcinoma gastric	2/2746 (0.1%)	2	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Adenocarcinoma of colon	1/2746 (0%)	1	4/2747 (0.1%)	4	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Adenocarcinoma pancreas	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Adrenal adenoma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atypical fibroxanthoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
B-cell lymphoma	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
B-cell small lymphocytic lymphoma	0/2746 (0%)	0	1/2747 (0%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Basal cell carcinoma	20/2746 (0.7%)	21	25/2747 (0.9%)	30	16/2745 (0.6%)	21	1/348 (0.3%)	1	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Basosquamous carcinoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Basosquamous carcinoma of skin	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Benign lung neoplasm	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder cancer	5/2746 (0.2%)	5	4/2747 (0.1%)	4	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder cancer recurrent	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder neoplasm	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder papilloma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder transitional cell carcinoma	2/2746 (0.1%)	2	3/2747 (0.1%)	3	1/2745 (0%)	1	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder transitional cell carcinoma stage II	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bone cancer	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bone giant cell tumour malignant	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bowen's disease	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain neoplasm	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain neoplasm benign	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain neoplasm malignant	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Breast cancer	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Breast cancer metastatic	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Breast cancer stage I	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchial carcinoma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Carcinoma in situ of skin	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cardiac myxoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cholangiocarcinoma	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic lymphocytic leukaemia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Clear cell endometrial carcinoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Clear cell renal cell carcinoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colon adenoma	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colon cancer	4/2746 (0.1%)	4	4/2747 (0.1%)	4	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colon cancer metastatic	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Colorectal adenocarcinoma	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diffuse large B-cell lymphoma stage IV	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ductal adenocarcinoma of pancreas	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Endometrial cancer	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Endometrial cancer stage III	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Follicular thyroid cancer	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gallbladder cancer	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastric cancer	2/2746 (0.1%)	2	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Gastric neoplasm	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Glioblastoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Glioblastoma multiforme	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Glioma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemangioma of liver	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hair follicle tumour benign	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic cancer	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic cancer metastatic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic neoplasm	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatocellular carcinoma	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
High-grade B-cell lymphoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intestinal adenocarcinoma	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intraductal papillary-mucinous carcinoma of pancreas	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intraductal proliferative breast lesion	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Invasive ductal breast carcinoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Keratoacanthoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Large cell lung cancer	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Leiomyosarcoma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Leukaemia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lipoma	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Liposarcoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung adenocarcinoma	2/2746 (0.1%)	2	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung adenocarcinoma stage 0	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung cancer metastatic	1/2746 (0%)	1	3/2747 (0.1%)	3	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung carcinoma cell type unspecified stage IV	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung neoplasm	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung neoplasm malignant	5/2746 (0.2%)	5	3/2747 (0.1%)	3	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung squamous cell carcinoma metastatic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lymphocytic leukaemia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lymphoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Malignant melanoma	2/2746 (0.1%)	2	4/2747 (0.1%)	4	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Malignant melanoma in situ	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Malignant neoplasm of ampulla of Vater	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Malignant neoplasm of renal pelvis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mantle cell lymphoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Marginal zone lymphoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meningioma	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Meningioma benign	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mesothelioma malignant	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastases to abdominal cavity	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastases to bone	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastases to central nervous system	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastases to liver	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastases to peritoneum	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastases to spine	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastatic gastric cancer	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastatic lymphoma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastatic malignant melanoma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastatic neoplasm	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metastatic squamous cell carcinoma	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myelodysplastic syndrome	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neoplasm	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neoplasm of orbit	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neuroendocrine carcinoma of the skin	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neuroendocrine tumour of the lung metastatic	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Non-small cell lung cancer metastatic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oesophageal adenocarcinoma	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oesophageal carcinoma	1/2746 (0%)	1	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oesophageal neoplasm	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Oral neoplasm	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatic carcinoma	3/2746 (0.1%)	3	3/2747 (0.1%)	3	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatic carcinoma metastatic	3/2746 (0.1%)	3	1/2747 (0%)	1	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pancreatic carcinoma recurrent	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Papillary renal cell carcinoma	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Papillary thyroid cancer	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Paranasal sinus benign neoplasm	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paranasal sinus neoplasm	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Penis carcinoma metastatic	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Plasma cell myeloma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostate cancer	16/2746 (0.6%)	16	10/2747 (0.4%)	10	11/2745 (0.4%)	11	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostate cancer metastatic	3/2746 (0.1%)	3	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostate cancer recurrent	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostate cancer stage I	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostate cancer stage II	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rectal adenocarcinoma	0/2746 (0%)	0	3/2747 (0.1%)	3	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rectal adenoma	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rectal cancer	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	1/55 (1.8%)	1	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Rectal cancer metastatic	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal cancer	3/2746 (0.1%)	3	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal cell carcinoma	1/2746 (0%)	1	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal neoplasm	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal oncocytoma	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Seborrhoeic keratosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	1	0/370 (0%)	1	0/347 (0%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skin cancer	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Small cell lung cancer	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Small cell lung cancer metastatic	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Small intestine carcinoma metastatic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Squamous cell carcinoma	7/2746 (0.3%)	8	8/2747 (0.3%)	8	10/2745 (0.4%)	12	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Squamous cell carcinoma of lung	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Squamous cell carcinoma of skin	5/2746 (0.2%)	6	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Squamous cell carcinoma of the cervix	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Squamous cell carcinoma of the tongue	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Testicular cancer metastatic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tongue cancer recurrent	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tongue neoplasm	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tongue neoplasm malignant stage unspecified	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tonsil cancer	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Transitional cell carcinoma	2/2746 (0.1%)	2	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tumour of ampulla of Vater	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Uterine cancer	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vulval cancer stage I	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nervous system disorders
Altered state of consciousness	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Amyotrophic lateral sclerosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aphasia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ataxia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Basal ganglia infarction	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain hypoxia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain injury	4/2746 (0.1%)	4	4/2747 (0.1%)	4	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain stem haemorrhage	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain stem infarction	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brain stem stroke	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Carotid arteriosclerosis	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Carotid artery occlusion	1/2746 (0%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Carotid artery stenosis	11/2746 (0.4%)	12	13/2747 (0.5%)	13	12/2745 (0.4%)	14	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Carpal tunnel syndrome	2/2746 (0.1%)	3	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Central nervous system lesion	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebellar infarction	2/2746 (0.1%)	2	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebellar stroke	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral arteriosclerosis	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral circulatory failure	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral haemorrhage	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral infarction	6/2746 (0.2%)	6	13/2747 (0.5%)	13	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral ischaemia	0/2746 (0%)	0	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral small vessel ischaemic disease	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebral venous thrombosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebrovascular accident	27/2746 (1%)	27	25/2747 (0.9%)	30	22/2745 (0.8%)	23	2/348 (0.6%)	2	3/370 (0.8%)	3	2/347 (0.6%)	2	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebrovascular disorder	1/2746 (0%)	1	3/2747 (0.1%)	3	2/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cerebrovascular insufficiency	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cervical cord compression	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cervical radiculopathy	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cervicobrachial syndrome	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic inflammatory demyelinating polyradiculoneuropathy	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cognitive disorder	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dementia Alzheimer's type	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic encephalopathy	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic neuropathy	5/2746 (0.2%)	7	1/2747 (0%)	1	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dizziness	2/2746 (0.1%)	2	2/2747 (0.1%)	2	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	1/55 (1.8%)	1	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dysarthria	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dyskinesia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Embolic cerebral infarction	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Embolic stroke	0/2746 (0%)	0	3/2747 (0.1%)	3	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Encephalopathy	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Epilepsy	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Essential tremor	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Facial paralysis	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemorrhagic cerebral infarction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemorrhagic stroke	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Headache	2/2746 (0.1%)	2	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hemiparaesthesia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hemiparesis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hepatic encephalopathy	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hydrocephalus	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypersomnia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypertensive encephalopathy	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypoxic-ischaemic encephalopathy	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intraventricular haemorrhage	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ischaemic cerebral infarction	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Ischaemic stroke	29/2746 (1.1%)	31	40/2747 (1.5%)	40	41/2745 (1.5%)	45	1/348 (0.3%)	1	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	1/54 (1.9%)	1	1/48 (2.1%)	1	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lacunar infarction	1/2746 (0%)	1	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lacunar stroke	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Leukoencephalopathy	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Loss of consciousness	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lumbar radiculopathy	1/2746 (0%)	1	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lumbosacral radiculopathy	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Memory impairment	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metabolic encephalopathy	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Migraine	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mixed dementia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Motor dysfunction	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myasthenia gravis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myelitis transverse	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Myelopathy	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neuralgia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neuralgic amyotrophy	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neuritis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neuropathy peripheral	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Normal pressure hydrocephalus	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paralysis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paraparesis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral paralysis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Polyneuropathy	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Presyncope	4/2746 (0.1%)	4	2/2747 (0.1%)	2	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Radiculopathy	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Reversible ischaemic neurological deficit	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Seizure	3/2746 (0.1%)	3	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Subarachnoid haemorrhage	1/2746 (0%)	1	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Syncope	8/2746 (0.3%)	10	10/2747 (0.4%)	10	8/2745 (0.3%)	9	0/348 (0%)	0	1/370 (0.3%)	1	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tension headache	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thalamic infarction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thrombotic cerebral infarction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Transient ischaemic attack	19/2746 (0.7%)	20	14/2747 (0.5%)	14	23/2745 (0.8%)	25	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Trigeminal neuralgia	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
VIth nerve paralysis	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular dementia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular encephalopathy	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vertebral artery stenosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vertebrobasilar insufficiency	2/2746 (0.1%)	2	2/2747 (0.1%)	2	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Product Issues
Device breakage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Device malfunction	1/2746 (0%)	1	3/2747 (0.1%)	3	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Device occlusion	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Device stimulation issue	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Psychiatric disorders
Adjustment disorder	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bipolar I disorder	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Completed suicide	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Confusional state	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Delirium	0/2746 (0%)	0	0/2747 (0%)	0	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Depression	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hallucination, visual	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Major depression	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mania	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mental disorder	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mental status changes	1/2746 (0%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Mood disorder due to a general medical condition	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paranoia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stress	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Suicidal ideation	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Suicide attempt	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal and urinary disorders
Acute kidney injury	24/2746 (0.9%)	24	18/2747 (0.7%)	18	22/2745 (0.8%)	24	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Azotaemia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder dysplasia	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder neck obstruction	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder outlet obstruction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bladder tamponade	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Calculus bladder	0/2746 (0%)	0	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Calculus urinary	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic kidney disease	1/2746 (0%)	1	6/2747 (0.2%)	6	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Cystitis haemorrhagic	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic nephropathy	2/2746 (0.1%)	5	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
End stage renal disease	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haematuria	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemorrhage urinary tract	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hydronephrosis	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nephrolithiasis	4/2746 (0.1%)	4	2/2747 (0.1%)	2	6/2745 (0.2%)	7	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nephropathy	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nephropathy toxic	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Neurogenic bladder	0/2746 (0%)	0	1/2747 (0%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Proteinuria	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal artery stenosis	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal colic	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal cyst	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal failure	4/2746 (0.1%)	4	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal impairment	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Renal tubular necrosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stag horn calculus	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stress urinary incontinence	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Tubulointerstitial nephritis	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ureteric stenosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ureterolithiasis	1/2746 (0%)	1	0/2747 (0%)	0	3/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urethral stenosis	2/2746 (0.1%)	2	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urinary incontinence	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urinary retention	2/2746 (0.1%)	2	4/2747 (0.1%)	5	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urinary tract obstruction	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Reproductive system and breast disorders
Acquired hydrocele	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Acquired phimosis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Benign prostatic hyperplasia	10/2746 (0.4%)	10	12/2747 (0.4%)	12	7/2745 (0.3%)	7	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	0/117 (0%)	0
Cystocele	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Genital haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Metrorrhagia	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Orchitis noninfective	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ovarian cyst	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostatic dysplasia	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostatitis	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Prostatomegaly	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Testicular mass	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Uterine prolapse	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vaginal prolapse	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/2746 (0%)	1	1/2747 (0%)	1	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Acute respiratory failure	8/2746 (0.3%)	8	7/2747 (0.3%)	7	9/2745 (0.3%)	9	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Asthma	3/2746 (0.1%)	3	2/2747 (0.1%)	2	4/2745 (0.1%)	7	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Asthma-chronic obstructive pulmonary disease overlap syndrome	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Atelectasis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchial hyperreactivity	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchiectasis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Bronchospasm	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic obstructive pulmonary disease	11/2746 (0.4%)	22	6/2747 (0.2%)	10	14/2745 (0.5%)	19	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Chronic respiratory failure	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dyspnoea	2/2746 (0.1%)	2	3/2747 (0.1%)	3	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Dyspnoea exertional	2/2746 (0.1%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Emphysema	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Epistaxis	0/2746 (0%)	0	3/2747 (0.1%)	3	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	1/113 (0.9%)	1	0/117 (0%)	0
Haemoptysis	2/2746 (0.1%)	2	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypoxia	0/2746 (0%)	0	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	2	0/370 (0%)	2	0/347 (0%)	2	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Interstitial lung disease	1/2746 (0%)	1	2/2747 (0.1%)	2	3/2745 (0.1%)	3	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Laryngeal oedema	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lower respiratory tract inflammation	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lung infiltration	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nasal polyps	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Nasal septum deviation	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Paranasal cyst	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pleural effusion	2/2746 (0.1%)	2	4/2747 (0.1%)	4	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pleurisy	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonia aspiration	1/2746 (0%)	1	1/2747 (0%)	1	3/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumonitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumothorax	1/2746 (0%)	1	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pneumothorax spontaneous	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary congestion	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary embolism	11/2746 (0.4%)	11	4/2747 (0.1%)	4	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary granuloma	1/2746 (0%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary haemorrhage	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary hypertension	2/2746 (0.1%)	2	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary infarction	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary mass	1/2746 (0%)	1	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Pulmonary oedema	2/2746 (0.1%)	2	2/2747 (0.1%)	2	6/2745 (0.2%)	7	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Respiratory arrest	0/2746 (0%)	0	2/2747 (0.1%)	2	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Respiratory disorder	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Respiratory failure	9/2746 (0.3%)	9	6/2747 (0.2%)	6	11/2745 (0.4%)	11	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Sleep apnoea syndrome	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	1/2746 (0%)	1	2/2747 (0.1%)	3	2/2745 (0.1%)	2	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Diabetic foot	10/2746 (0.4%)	10	9/2747 (0.3%)	9	13/2745 (0.5%)	14	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	0/117 (0%)	0
Diabetic ulcer	0/2746 (0%)	0	1/2747 (0%)	3	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Eczema	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Ischaemic skin ulcer	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Lichen sclerosus	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Psoriasis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skin necrosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Skin ulcer	5/2746 (0.2%)	8	7/2747 (0.3%)	7	4/2745 (0.1%)	4	2/348 (0.6%)	2	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Stasis dermatitis	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Urticaria	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Surgical and medical procedures
Atrial appendage closure	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Vascular disorders
Accelerated hypertension	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aortic aneurysm	7/2746 (0.3%)	7	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aortic aneurysm rupture	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aortic stenosis	2/2746 (0.1%)	2	3/2747 (0.1%)	3	6/2745 (0.2%)	6	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Aortic thrombosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arteriosclerosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Arteriovenous fistula	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Blood pressure inadequately controlled	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Brachiocephalic artery stenosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Circulatory collapse	3/2746 (0.1%)	3	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Deep vein thrombosis	4/2746 (0.1%)	4	2/2747 (0.1%)	2	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Embolism arterial	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Extremity necrosis	2/2746 (0.1%)	3	6/2747 (0.2%)	8	4/2745 (0.1%)	5	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	1/55 (1.8%)	1	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Femoral artery aneurysm	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haematoma	3/2746 (0.1%)	3	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	1/100 (1%)	1	0/113 (0%)	0	0/117 (0%)	0
Haemorrhage	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Haemorrhagic vasculitis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypertension	2/2746 (0.1%)	2	5/2747 (0.2%)	5	11/2745 (0.4%)	12	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypertensive crisis	4/2746 (0.1%)	6	0/2747 (0%)	0	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypertensive emergency	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypertensive urgency	1/2746 (0%)	1	2/2747 (0.1%)	2	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypotension	4/2746 (0.1%)	4	2/2747 (0.1%)	2	10/2745 (0.4%)	10	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Hypovolaemic shock	1/2746 (0%)	1	3/2747 (0.1%)	3	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Iliac artery occlusion	0/2746 (0%)	0	0/2747 (0%)	0	2/2745 (0.1%)	2	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Iliac artery rupture	0/2746 (0%)	0	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Iliac artery stenosis	1/2746 (0%)	1	1/2747 (0%)	1	2/2745 (0.1%)	2	0/348 (0%)	0	1/370 (0.3%)	1	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Intermittent claudication	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Leriche syndrome	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Orthostatic hypotension	5/2746 (0.2%)	5	3/2747 (0.1%)	3	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral arterial occlusive disease	16/2746 (0.6%)	19	20/2747 (0.7%)	23	22/2745 (0.8%)	25	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral artery aneurysm	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral artery occlusion	3/2746 (0.1%)	4	3/2747 (0.1%)	3	8/2745 (0.3%)	9	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	1/117 (0.9%)	1
Peripheral artery stenosis	1/2746 (0%)	1	5/2747 (0.2%)	7	5/2745 (0.2%)	5	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral artery thrombosis	3/2746 (0.1%)	3	2/2747 (0.1%)	2	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	1/347 (0.3%)	1	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral embolism	0/2746 (0%)	0	1/2747 (0%)	1	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral ischaemia	17/2746 (0.6%)	18	13/2747 (0.5%)	18	10/2745 (0.4%)	10	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral vascular disorder	4/2746 (0.1%)	4	3/2747 (0.1%)	5	4/2745 (0.1%)	4	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Peripheral venous disease	1/2746 (0%)	1	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Shock haemorrhagic	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Subclavian artery occlusion	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Subclavian artery stenosis	1/2746 (0%)	1	1/2747 (0%)	1	0/2745 (0%)	0	1/348 (0.3%)	1	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Thrombosis	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Varicose ulceration	1/2746 (0%)	1	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Varicose vein	1/2746 (0%)	2	1/2747 (0%)	1	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Venous thrombosis	0/2746 (0%)	0	0/2747 (0%)	0	1/2745 (0%)	1	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Venous thrombosis limb	2/2746 (0.1%)	2	0/2747 (0%)	0	0/2745 (0%)	0	0/348 (0%)	0	0/370 (0%)	0	0/347 (0%)	0	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	0/100 (0%)	0	0/113 (0%)	0	0/117 (0%)	0
Other (Not Including Serious) Adverse Events
	Ertugliflozin 5 mg (Overall Cardiovascular Study)		Ertugliflozin 15 mg (Overall Cardiovascular Study)		Placebo (Overall Cardiovascular Study)		Ertugliflozin 5 mg (Insulin +/- Metformin Sub-study)		Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)		Placebo (Insulin +/- Metformin Glycemic Sub-study)		Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)		Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)		Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)		Placebo (Metformin With Sulfonylurea Glycemic Sub-study)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1405/2746 (51.2%)		1389/2747 (50.6%)		1395/2745 (50.8%)		127/348 (36.5%)		144/370 (38.9%)		135/347 (38.9%)		10/55 (18.2%)		4/54 (7.4%)		9/48 (18.8%)		24/100 (24%)		32/113 (28.3%)		26/117 (22.2%)
Gastrointestinal disorders
Diarrhoea	132/2746 (4.8%)	163	138/2747 (5%)	161	126/2745 (4.6%)	153	7/348 (2%)	7	9/370 (2.4%)	11	8/347 (2.3%)	8	0/55 (0%)	0	0/54 (0%)	0	1/48 (2.1%)	1	2/100 (2%)	2	3/113 (2.7%)	3	0/117 (0%)	0
Infections and infestations
Nasopharyngitis	178/2746 (6.5%)	249	204/2747 (7.4%)	272	186/2745 (6.8%)	244	4/348 (1.1%)	4	13/370 (3.5%)	13	11/347 (3.2%)	12	1/55 (1.8%)	1	0/54 (0%)	0	2/48 (4.2%)	4	2/100 (2%)	2	5/113 (4.4%)	5	3/117 (2.6%)	3
Upper respiratory tract infection	197/2746 (7.2%)	277	177/2747 (6.4%)	257	203/2745 (7.4%)	324	8/348 (2.3%)	8	10/370 (2.7%)	11	9/347 (2.6%)	9	0/55 (0%)	0	0/54 (0%)	0	0/48 (0%)	0	3/100 (3%)	3	2/113 (1.8%)	2	4/117 (3.4%)	4
Urinary tract infection	256/2746 (9.3%)	378	262/2747 (9.5%)	354	211/2745 (7.7%)	301	8/348 (2.3%)	8	9/370 (2.4%)	10	7/347 (2%)	7	1/55 (1.8%)	2	1/54 (1.9%)	1	0/48 (0%)	0	1/100 (1%)	1	4/113 (3.5%)	5	3/117 (2.6%)	4
Metabolism and nutrition disorders
Hyperglycaemia	106/2746 (3.9%)	158	96/2747 (3.5%)	201	178/2745 (6.5%)	283	5/348 (1.4%)	7	9/370 (2.4%)	13	6/347 (1.7%)	7	0/55 (0%)	0	0/54 (0%)	0	2/48 (4.2%)	2	3/100 (3%)	3	2/113 (1.8%)	2	1/117 (0.9%)	1
Hypoglycaemia	883/2746 (32.2%)	10056	854/2747 (31.1%)	9474	884/2745 (32.2%)	11591	101/348 (29%)	400	112/370 (30.3%)	541	109/347 (31.4%)	559	3/55 (5.5%)	4	3/54 (5.6%)	3	0/48 (0%)	0	13/100 (13%)	23	19/113 (16.8%)	110	14/117 (12%)	49
Musculoskeletal and connective tissue disorders
Back pain	133/2746 (4.8%)	144	138/2747 (5%)	157	143/2745 (5.2%)	160	2/348 (0.6%)	2	2/370 (0.5%)	2	2/347 (0.6%)	2	2/55 (3.6%)	2	0/54 (0%)	0	2/48 (4.2%)	2	1/100 (1%)	1	1/113 (0.9%)	1	2/117 (1.7%)	2
Nervous system disorders
Dizziness	139/2746 (5.1%)	174	141/2747 (5.1%)	179	89/2745 (3.2%)	107	8/348 (2.3%)	8	9/370 (2.4%)	10	4/347 (1.2%)	4	1/55 (1.8%)	1	0/54 (0%)	0	0/48 (0%)	0	2/100 (2%)	2	4/113 (3.5%)	4	1/117 (0.9%)	1
Vascular disorders
Hypertension	133/2746 (4.8%)	218	148/2747 (5.4%)	272	168/2745 (6.1%)	343	5/348 (1.4%)	5	4/370 (1.1%)	4	2/347 (0.6%)	2	2/55 (3.6%)	2	0/54 (0%)	0	2/48 (4.2%)	2	4/100 (4%)	4	2/113 (1.8%)	2	3/117 (2.6%)	3

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure to the sponsor at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, investigator agrees to delay the disclosure for an additional 60 days. Investigator will, on request, remove any previously undisclosed Confidential Information (other than the Study results themselves) before disclosure.