A Study to Assess Cardiovascular Outcomes Following Treatment With Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (MK-3102-018)

• Sponsor: Merck Sharp & Dohme Corp. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01703208
• Collaborator: (none)
• Enrollment: 4,202
• Arms: 2
• Actual Duration (Months): 53.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the cardiovascular (CV) safety profile of omarigliptin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that treatment with omarigliptin 25 mg once weekly is non-inferior to treatment with placebo and active comparators across the omarigliptin program with regard to the risk of developing a confirmed event in the primary CV composite endpoint.

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

Detailed Description

The trial was amended to extend the length of the trial in order to meet FDA requirements for the post-approval assessment of cardiovascular (CV) safety. The trial now contains 2 time intervals: Period 1 and Period 2. Period 1 refers to the time interval up to this recent protocol amendment and Period 2, the time interval from this protocol amendment until the end of the study. Participants in Period 1 will be re-consented and continue into Period 2. If required, additional participants will be enrolled in Period 2. Stage 1 refers to the prefiling United States Food and Drug Administration (US FDA) requirement to rule out a 80% increased CV risk. Stage 2 refers to the US FDA post-marketing requirement to rule out a 30% increased CV risk. The Stage 1 assessment of CV risk occurred during Period 1 and was based on a meta-analysis of major adverse CV events (MACE) and unstable angina across the omarigliptin Phase 2/Phase 3 program. The Stage 2 assessment will be based on MACE in P018 alone including CV events from both Period 1 and Period 2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4202 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess Cardiovascular Outcomes Following Treatment With MK-3102 in Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: Oct 5, 2012
• Actual Primary Completion Date: May 13, 2016
• Actual Study Completion Date: Mar 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omarigliptin Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly
Placebo Comparator: Placebo Matching placebo to omarigliptin capsule or tablet administered orally once weekly	Drug: Placebo; Matching placebo to omarigliptin capsule or tablet administered orally once weekly

Outcome Measures

Primary Outcome Measures

1. Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina) [Up to 156 weeks]

   Participants with confirmed MACE-plus events (confirmed cardiovascular, CV-related death, nonfatal myocardial infarction [MI], nonfatal stroke, or hospitalization due to unstable angina). In the MK-3102-018 study, MACE plus events had a data cut-off date of April 15, 2015.

2. Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) [Up to 179 weeks]

   Participants with an Event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke).

3. Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) [Up to 179 weeks]

   Participants with an event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke). Person-years were calculated as the sum of all participants' follow-up time to first event.

4. Change From Baseline in Hemoglobin A1C (A1C) at Week 18 [Baseline and Week 18]

   A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.

5. Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin) [Baseline and Week 18]

   A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.

6. Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change [Up to Week 18]

   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.

7. Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change [Up to Week 18]

   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.

Secondary Outcome Measures

1. Number of Participants With an Event of CV-Related Death [Up to 179 weeks]

   Participants with adjudicated and confirmed AEs of cardiovascular-related death.

2. Number of Participants With an Event Per 100 Person-Years of CV-Related Death [Up to 179 weeks]

   Participants with adjudicated and confirmed AEs of cardiovascular-related death. Person-years were calculated as the sum of all participants' follow-up time to event.

3. Number of Participants With an Event of First MI (Fatal and Non-fatal) [Up to 179 weeks]

   Participants with adjudicated and confirmed AEs of fatal and non-fatal MI.

4. Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal) [Up to 179 weeks]

   Participants with adjudicated and confirmed AEs of fatal and non-fatal MI. Person-years were calculated as the sum of all participants' follow-up time to first event.

5. Number of Participants With an Event of Stroke (Fatal and Non-fatal) [Up to 179 weeks]

   Participants with adjudicated and confirmed AEs fatal and non-fatal stroke.

6. Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal) [Up to 179 weeks]

   Participants with adjudicated and confirmed AEs fatal and non-fatal stroke. Person-years were calculated as the sum of all participants' follow-up time to event.

7. Number of Participants With an Event of All-Cause Death [Up to 179 weeks]

   All-cause death was death from any cause.

8. Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death [Up to 179 weeks]

   All-cause death was death for any cause. Person-years were calculated as the sum of all participants' follow-up time to event.

9. Change From Baseline in A1C at Week 142 [Baseline and Week 142]

   A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 142 A1C minus the Week 0 A1C.

10. Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at 4 Months [4 months]

    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).

11. Change From Baseline in Fasting Plasma Glucose (FPG) at 4 Months [Baseline and 4 months]

    This change from baseline reflects the Month 4 FPG minus the Week 0 FPG.

12. Time to Initiation of Long-Term Insulin Therapy in Participants Not Receiving Insulin at Baseline [Up to 179 weeks]

    Long-term insulin therapy was defined as a continuous period of insulin use of more than 3 months.

13. Percentage of Participants Who Experienced at Least One Adverse Event [Up to 234 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.

14. Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event [Up to 212 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.

15. Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin [Baseline and Week 18]

    This change from baseline reflects the Week 18 FPG minus the Week 0 FPG.

16. Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin [18 weeks]

    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Analysis was performed with multiple data imputation.

Other Outcome Measures

1. Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory) [Up to 179 weeks]

   Participants with adjudicated and confirmed events of first hospitalization for heart failure.

2. Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory) [Up to 179 weeks]

   Participants with adjudicated and confirmed events of first hospitalization for heart failure. Person-years were calculated as the sum of all participants' follow-up time to event.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosed with type 2 diabetes mellitus

• Is on one of the following diabetes treatment regimens that is stable for at least 12 weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C range for that treatment regimen:

1. A1C >= 6.5% and <= 10.0% (>=48 mmol/mol and <=86 mmol/mol) on: (a) diet or exercise alone (not on antihyperglycemic agent [AHA] for >= 12 weeks) OR (b) monotherapy with metformin (MF), pioglitazone (PIO) or an alpha-glucosidase inhibitor (AGI) or a sodium-glucose cotransporter inhibitor (SGLT2i) OR (c) dual combination therapy with MF, PIO, AGI or SGLT2i OR

2. A1C >= 7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on (a) monotherapy with a sulfonylurea or meglitinide OR (b) dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i OR

3. A1C >=7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on one of the following insulin regimens (with or without metformin): (a) basal insulin (e.g.; insulin glargine, insulin detemir, NPH insulin, degludec) OR (b) prandial insulin (e.g. regular, aspart, lispro, glulisine) OR (c) basal/prandial insulin regimen consisting of multiple dose insulin injections of basal and prandial insulin or the use of pre-mixed insulin (e.g., Novolog 70/30®, Novolin 70/30®, Humalog 75/25®, or Humulin 70/30®

• Pre-existing vascular disease (coronary artery disease, ischemic cerebrovascular disease, atherosclerotic peripheral artery disease)

• (1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug.

Exclusion Criteria:

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

• Treated with rosiglitazone, a dipeptidyl peptidase-IV (DPP-4) inhibitor, or a glucagon-like peptide-1 (GLP-1) receptor agonist within 12 weeks prior to study participation or previously treated with omarigliptin

• On a weight loss program and is not in the maintenance phase or has been on a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation

• Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease

• Human immunodeficiency virus (HIV) as assessed by medical history

• New or worsening coronary heart disease, congestive heart failure, myocardial infarction, unstable angina, coronary artery intervention, stroke, or transient ischemic neurological disorder within the past 3 months

• History of malignancy <=5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer

• Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

• Pregnant or breast feeding, or is expecting to conceive or donate eggs during the trial, including 21 days following the last dose of study drug

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme Corp.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01703208
• Other Study ID Numbers: 3102-018; 2012-002414-39; MK-3102-018
• First Posted: Oct 10, 2012
• Last Update Posted: Nov 6, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	A total of 559 sites received IEC/IRB approval in 40 countries and 547 were shipped clinical supplies. Of the 559 sites, 525 screened at least 1 participant. An insulin sub-study of MK-3102-018 was performed and included the sub-population of participants receiving ≥20 units/day of background insulin with or without metformin.
Pre-assignment Detail	On April 8, 2016, Merck & Co. Inc. announced that it would not submit marketing applications for omarigliptin (MK-3102) in the US and Europe for business reasons only. Because of this decision, the MK-3102-018 study was terminated early on May 13, 2016. Due to delays in study close-out the Last-Participant-Last-Visit occurred on March 22, 2017.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Period Title: Overall Study
STARTED	2100	2102
Treated	2092	2100
COMPLETED	0	0
NOT COMPLETED	2100	2102

Baseline Characteristics

Arm/Group Title	Omarigliptin 25 mg	Placebo	Total
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.	Total of all reporting groups
Overall Participants	2100	2102	4202
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.7 (8.5)	63.6 (8.5)	63.6 (8.5)
Sex: Female, Male (Count of Participants)
Female	639 30.4%	615 29.3%	1254 29.8%
Male	1461 69.6%	1487 70.7%	2948 70.2%
Hemoglobin A1C % (Percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent]	7.99 (0.86)	8.03 (0.89)	8.01 (0.87)
Fasting Plasma Glucose (FPG) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	184.1 (52.2)	179.5 (45.7)	180.4 (47.8)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina)
Description	Participants with confirmed MACE-plus events (confirmed cardiovascular, CV-related death, nonfatal myocardial infarction [MI], nonfatal stroke, or hospitalization due to unstable angina). In the MK-3102-018 study, MACE plus events had a data cut-off date of April 15, 2015.
Time Frame	Up to 156 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who took at least one dose of blinded study medication and were evaluated for MACE-plus events.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2090	2100
Number [Participants]	66 3.1%	70 3.3%

2. Primary Outcome

Title	Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke)
Description	Participants with an Event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke).
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who took at least one dose of blinded trial medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants]	114 5.4%	114 5.4%

3. Primary Outcome

Title	Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke)
Description	Participants with an event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke). Person-years were calculated as the sum of all participants' follow-up time to first event.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who took at least one dose of blinded trial medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants/100 Person-years]	2.96 0.1%	2.97 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the proportional hazards model that includes treatment as an explanatory factor.

4. Primary Outcome

Title	Change From Baseline in Hemoglobin A1C (A1C) at Week 18
Description	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Least Squares Mean (95% Confidence Interval) [Percent]	-0.58 (0.82)	-0.16 (0.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.48 to -0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin)
Description	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population consists of all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	535	509
Least Squares Mean (95% Confidence Interval) [Percentage]	-0.50	-0.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Longitudinal data analysis
	Comments	Longitudinal data analysis model including terms for treatment, time and the interaction of time by treatment.
Method of Estimation	Estimation Parameter	Difference in the LS Means vs Placebo
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change
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 Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	535	509
Number [Percentage of participants]	48.8 2.3%	49.9 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percent vs. Placebo
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -7.2 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method. The 95% CI was computed only for those endpoints with at least 4 participants having events in one or more treatment groups.

7. Primary Outcome

Title	Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change
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 Week 18

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	535	509
Number [Percentage of participants]	1.1 0.1%	0.8 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage vs. Placebo
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method. The 95% CI was computed only for those endpoints with at least 4 participants having events in one or more treatment groups.

8. Secondary Outcome

Title	Number of Participants With an Event of CV-Related Death
Description	Participants with adjudicated and confirmed AEs of cardiovascular-related death.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants]	37 1.8%	35 1.7%

9. Secondary Outcome

Title	Number of Participants With an Event Per 100 Person-Years of CV-Related Death
Description	Participants with adjudicated and confirmed AEs of cardiovascular-related death. Person-years were calculated as the sum of all participants' follow-up time to event.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants/100 person-years]	0.94 0%	0.89 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the proportional hazards model that includes treatment as an explanatory factor.

10. Secondary Outcome

Title	Number of Participants With an Event of First MI (Fatal and Non-fatal)
Description	Participants with adjudicated and confirmed AEs of fatal and non-fatal MI.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants]	52 2.5%	60 2.9%

11. Secondary Outcome

Title	Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal)
Description	Participants with adjudicated and confirmed AEs of fatal and non-fatal MI. Person-years were calculated as the sum of all participants' follow-up time to first event.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants/100 person-years]	1.34 0.1%	1.55 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the proportional hazards model that includes treatment as an explanatory factor.

12. Secondary Outcome

Title	Number of Participants With an Event of Stroke (Fatal and Non-fatal)
Description	Participants with adjudicated and confirmed AEs fatal and non-fatal stroke.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants]	32 1.5%	34 1.6%

13. Secondary Outcome

Title	Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal)
Description	Participants with adjudicated and confirmed AEs fatal and non-fatal stroke. Person-years were calculated as the sum of all participants' follow-up time to event.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants/100 person-years]	0.82 0%	0.88 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the proportional hazards model that includes treatment as an explanatory factor.

14. Secondary Outcome

Title	Number of Participants With an Event of All-Cause Death
Description	All-cause death was death from any cause.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who took at least one dose of blinded trial medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants]	64 3%	50 2.4%

15. Secondary Outcome

Title	Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death
Description	All-cause death was death for any cause. Person-years were calculated as the sum of all participants' follow-up time to event.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants/100 Person-years]	1.63 0.1%	1.28 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the proportional hazards model that includes treatment as an explanatory factor.

16. Secondary Outcome

Title	Change From Baseline in A1C at Week 142
Description	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 142 A1C minus the Week 0 A1C.
Time Frame	Baseline and Week 142

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Least Squares Mean (95% Confidence Interval) [Percent]	-0.36 (0.06)	-0.06 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in the Least Squares Means
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.46 to -0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Longitudinal Data Analysis (LDA) model including terms for treatment, time, and the interaction of time by treatment.

17. Secondary Outcome

Title	Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at 4 Months
Description	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

Data for this efficacy endpoint was not collected, analyzed or summarized.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	0	0

18. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at 4 Months
Description	This change from baseline reflects the Month 4 FPG minus the Week 0 FPG.
Time Frame	Baseline and 4 months

Outcome Measure Data

Analysis Population Description

Data for this efficacy endpoint was not collected, analyzed or summarized.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	0	0

19. Secondary Outcome

Title	Time to Initiation of Long-Term Insulin Therapy in Participants Not Receiving Insulin at Baseline
Description	Long-term insulin therapy was defined as a continuous period of insulin use of more than 3 months.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

Data for this efficacy endpoint was not collected, analyzed or summarized.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	0	0

20. Secondary Outcome

Title	Percentage of Participants Who Experienced at Least One Adverse Event
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 234 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Percentage of participants]	78.3 3.7%	76.8 3.7%

21. Secondary Outcome

Title	Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event
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 212 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Percentage of participants]	4.1 0.2%	3.6 0.2%

22. Secondary Outcome

Title	Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin
Description	This change from baseline reflects the Week 18 FPG minus the Week 0 FPG.
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	535	509
Least Squares Mean (95% Confidence Interval) [mg/dL]	-6.8	-3.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.421
	Comments
	Method	Longitudinal constrained data analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in the least squares means
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -10.8 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on a LDA model including terms for treatment, time and the interaction of time by treatment.

23. Secondary Outcome

Title	Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin
Description	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Analysis was performed with multiple data imputation.
Time Frame	18 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	535	509
Number (95% Confidence Interval) [Percentage of participants]	22.0 1%	10.2 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Estimated using standard multiple imputation techniques.
	Method	Miettinen & Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Between group rate difference
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95%; 6.9 to 16.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Other Pre-specified Outcome

Title	Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory)
Description	Participants with adjudicated and confirmed events of first hospitalization for heart failure.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants]	20 1%	33 1.6%

25. Other Pre-specified Outcome

Title	Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory)
Description	Participants with adjudicated and confirmed events of first hospitalization for heart failure. Person-years were calculated as the sum of all participants' follow-up time to event.
Time Frame	Up to 179 weeks

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all participants who took at least one dose of blinded study medication.

Arm/Group Title	Omarigliptin 25 mg	Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly	Matching placebo to omarigliptin capsule or tablet administered once weekly.
Measure Participants	2092	2100
Number [Participants/100 Person-years]	0.51 0%	0.85 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omarigliptin 25 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.35 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the proportional hazards model that includes treatment as an explanatory factor.

Adverse Events

Time Frame	Up to 234 weeks
Adverse Event Reporting Description	Participants with serious adverse events with an incidence > 0% and with >5% non-serous adverse events in one or more treatment groups during the Treatment Period + Post-Treatment Follow-up including Post-21 days after last dose of blinded study treatment for randomized participants receiving one or more doses of study treatment.
Arm/Group Title	Omarigliptin 25 mg		Placebo
Arm/Group Description	Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly		Matching placebo to omarigliptin capsule or tablet administered once weekly.
All Cause Mortality
	Omarigliptin 25 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Omarigliptin 25 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	512/2092 (24.5%)		503/2100 (24%)
Blood and lymphatic system disorders
Agranulocytosis	1/2092 (0%)	1	0/2100 (0%)	0
Anaemia	6/2092 (0.3%)	6	4/2100 (0.2%)	4
Coagulation factor deficiency	1/2092 (0%)	1	0/2100 (0%)	0
Disseminated intravascular coagulation	2/2092 (0.1%)	2	0/2100 (0%)	0
Haemorrhagic anaemia	0/2092 (0%)	0	2/2100 (0.1%)	3
Iron deficiency anaemia	2/2092 (0.1%)	2	0/2100 (0%)	0
Lymphadenitis	1/2092 (0%)	1	0/2100 (0%)	0
Pancytopenia	0/2092 (0%)	0	1/2100 (0%)	1
Splenic infarction	2/2092 (0.1%)	2	0/2100 (0%)	0
Thrombocytosis	0/2092 (0%)	0	1/2100 (0%)	1
Cardiac disorders
Acute coronary syndrome	3/2092 (0.1%)	3	7/2100 (0.3%)	7
Acute myocardial infarction	30/2092 (1.4%)	35	27/2100 (1.3%)	28
Angina pectoris	27/2092 (1.3%)	29	31/2100 (1.5%)	36
Angina unstable	33/2092 (1.6%)	39	42/2100 (2%)	46
Aortic valve stenosis	5/2092 (0.2%)	5	1/2100 (0%)	1
Arteriosclerosis coronary artery	1/2092 (0%)	1	0/2100 (0%)	0
Atrial fibrillation	14/2092 (0.7%)	14	16/2100 (0.8%)	17
Atrial flutter	5/2092 (0.2%)	7	3/2100 (0.1%)	3
Atrial tachycardia	0/2092 (0%)	0	1/2100 (0%)	1
Atrioventricular block	1/2092 (0%)	1	1/2100 (0%)	1
Atrioventricular block complete	3/2092 (0.1%)	3	0/2100 (0%)	0
Bradyarrhythmia	1/2092 (0%)	1	0/2100 (0%)	0
Bradycardia	2/2092 (0.1%)	2	1/2100 (0%)	1
Cardiac aneurysm	1/2092 (0%)	1	0/2100 (0%)	0
Cardiac arrest	9/2092 (0.4%)	9	4/2100 (0.2%)	4
Cardiac failure	17/2092 (0.8%)	21	12/2100 (0.6%)	12
Cardiac failure acute	6/2092 (0.3%)	6	4/2100 (0.2%)	4
Cardiac failure chronic	7/2092 (0.3%)	8	3/2100 (0.1%)	3
Cardiac failure congestive	14/2092 (0.7%)	16	20/2100 (1%)	25
Cardio-respiratory arrest	0/2092 (0%)	0	3/2100 (0.1%)	3
Cardiogenic shock	2/2092 (0.1%)	2	4/2100 (0.2%)	4
Cardiomyopathy	0/2092 (0%)	0	2/2100 (0.1%)	2
Cardiopulmonary failure	1/2092 (0%)	1	4/2100 (0.2%)	5
Conduction disorder	1/2092 (0%)	1	0/2100 (0%)	0
Cor pulmonale	0/2092 (0%)	0	1/2100 (0%)	1
Coronary artery disease	22/2092 (1.1%)	24	23/2100 (1.1%)	24
Coronary artery insufficiency	0/2092 (0%)	0	1/2100 (0%)	1
Coronary artery occlusion	3/2092 (0.1%)	3	4/2100 (0.2%)	4
Coronary artery stenosis	9/2092 (0.4%)	9	6/2100 (0.3%)	6
Ischaemic cardiomyopathy	1/2092 (0%)	1	1/2100 (0%)	1
Left ventricular failure	1/2092 (0%)	1	2/2100 (0.1%)	2
Myocardial infarction	19/2092 (0.9%)	19	17/2100 (0.8%)	19
Myocardial ischaemia	5/2092 (0.2%)	6	3/2100 (0.1%)	3
Myocardial reperfusion injury	1/2092 (0%)	1	0/2100 (0%)	0
Pericardial effusion	0/2092 (0%)	0	1/2100 (0%)	1
Right ventricular failure	1/2092 (0%)	1	0/2100 (0%)	0
Silent myocardial infarction	2/2092 (0.1%)	2	1/2100 (0%)	1
Sinus node dysfunction	1/2092 (0%)	1	0/2100 (0%)	0
Supraventricular tachycardia	3/2092 (0.1%)	4	1/2100 (0%)	1
Ventricular arrhythmia	0/2092 (0%)	0	1/2100 (0%)	1
Ventricular extrasystoles	1/2092 (0%)	1	3/2100 (0.1%)	3
Ventricular fibrillation	3/2092 (0.1%)	3	0/2100 (0%)	0
Ventricular tachyarrhythmia	1/2092 (0%)	1	0/2100 (0%)	0
Ventricular tachycardia	2/2092 (0.1%)	2	3/2100 (0.1%)	4
Trifascicular block	1/2092 (0%)	1	0/2100 (0%)	0
Congenital, familial and genetic disorders
Congenital claw toe	1/2092 (0%)	1	0/2100 (0%)	0
Encephalocele	0/2092 (0%)	0	1/2100 (0%)	1
Ear and labyrinth disorders
Deafness neurosensory	0/2092 (0%)	0	2/2100 (0.1%)	2
Deafness unilateral	0/2092 (0%)	0	1/2100 (0%)	1
Vertigo	2/2092 (0.1%)	2	0/2100 (0%)	0
Vertigo positional	0/2092 (0%)	0	1/2100 (0%)	1
Vestibular disorder	1/2092 (0%)	1	0/2100 (0%)	0
Endocrine disorders
Goitre	1/2092 (0%)	1	1/2100 (0%)	1
Eye disorders
Cataract	0/2092 (0%)	0	2/2100 (0.1%)	2
Keratitis	1/2092 (0%)	1	0/2100 (0%)	0
Retinal detachment	0/2092 (0%)	0	2/2100 (0.1%)	3
Retinal haemorrhage	0/2092 (0%)	0	1/2100 (0%)	1
Retinal tear	1/2092 (0%)	1	0/2100 (0%)	0
Vitreous haemorrhage	0/2092 (0%)	0	2/2100 (0.1%)	2
Gastrointestinal disorders
Abdominal hernia	2/2092 (0.1%)	2	1/2100 (0%)	1
Abdominal pain	0/2092 (0%)	0	1/2100 (0%)	1
Acquired oesophageal web	1/2092 (0%)	1	0/2100 (0%)	0
Anal spasm	0/2092 (0%)	0	1/2100 (0%)	1
Chronic gastritis	0/2092 (0%)	0	1/2100 (0%)	1
Colitis	0/2092 (0%)	0	1/2100 (0%)	1
Constipation	1/2092 (0%)	1	0/2100 (0%)	0
Crohn's disease	0/2092 (0%)	0	1/2100 (0%)	1
Diabetic gastroenteropathy	0/2092 (0%)	0	1/2100 (0%)	1
Diabetic gastroparesis	0/2092 (0%)	0	1/2100 (0%)	1
Diarrhoea	1/2092 (0%)	1	1/2100 (0%)	1
Diverticular perforation	0/2092 (0%)	0	1/2100 (0%)	1
Diverticulum	0/2092 (0%)	0	1/2100 (0%)	1
Duodenal ulcer	1/2092 (0%)	1	0/2100 (0%)	0
Enterovesical fistula	1/2092 (0%)	1	0/2100 (0%)	0
Food poisoning	1/2092 (0%)	1	1/2100 (0%)	1
Gastric polyps	1/2092 (0%)	1	0/2100 (0%)	0
Gastric ulcer	2/2092 (0.1%)	2	1/2100 (0%)	1
Gastric ulcer haemorrhage	2/2092 (0.1%)	2	1/2100 (0%)	1
Gastric varices haemorrhage	0/2092 (0%)	0	1/2100 (0%)	1
Gastritis	1/2092 (0%)	1	1/2100 (0%)	1
Gastritis erosive	1/2092 (0%)	1	0/2100 (0%)	0
Gastroduodenitis	0/2092 (0%)	0	1/2100 (0%)	1
Gastrointestinal disorder	1/2092 (0%)	1	1/2100 (0%)	1
Gastrointestinal haemorrhage	2/2092 (0.1%)	2	2/2100 (0.1%)	2
Gastrointestinal ulcer haemorrhage	0/2092 (0%)	0	1/2100 (0%)	1
Gastrooesophageal reflux disease	0/2092 (0%)	0	1/2100 (0%)	1
Ileus	0/2092 (0%)	0	1/2100 (0%)	1
Ileus paralytic	1/2092 (0%)	1	1/2100 (0%)	1
Impaired gastric emptying	1/2092 (0%)	1	0/2100 (0%)	0
Incarcerated umbilical hernia	0/2092 (0%)	0	1/2100 (0%)	1
Inguinal hernia	5/2092 (0.2%)	6	2/2100 (0.1%)	2
Intestinal obstruction	2/2092 (0.1%)	2	0/2100 (0%)	0
Large intestine polyp	1/2092 (0%)	1	4/2100 (0.2%)	4
Lower gastrointestinal haemorrhage	0/2092 (0%)	0	2/2100 (0.1%)	3
Noninfective gingivitis	1/2092 (0%)	1	0/2100 (0%)	0
Oesophagitis	3/2092 (0.1%)	3	0/2100 (0%)	0
Pancreatic cyst	1/2092 (0%)	1	0/2100 (0%)	0
Pancreatitis	1/2092 (0%)	1	1/2100 (0%)	1
Pancreatitis acute	2/2092 (0.1%)	2	1/2100 (0%)	1
Pancreatitis chronic	0/2092 (0%)	0	1/2100 (0%)	1
Peptic ulcer	1/2092 (0%)	1	0/2100 (0%)	0
Rectal haemorrhage	0/2092 (0%)	0	2/2100 (0.1%)	2
Retroperitoneal haematoma	1/2092 (0%)	1	0/2100 (0%)	0
Small intestinal obstruction	0/2092 (0%)	0	2/2100 (0.1%)	2
Strangulated umbilical hernia	1/2092 (0%)	1	0/2100 (0%)	0
Upper gastrointestinal haemorrhage	1/2092 (0%)	1	3/2100 (0.1%)	3
Vomiting	0/2092 (0%)	0	1/2100 (0%)	1
General disorders
Cardiac death	0/2092 (0%)	0	1/2100 (0%)	1
Chest pain	6/2092 (0.3%)	8	1/2100 (0%)	1
Complication associated with device	2/2092 (0.1%)	2	1/2100 (0%)	1
Death	4/2092 (0.2%)	4	0/2100 (0%)	0
Multiple organ dysfunction syndrome	5/2092 (0.2%)	5	1/2100 (0%)	1
Non-cardiac chest pain	5/2092 (0.2%)	5	8/2100 (0.4%)	10
Sudden cardiac death	0/2092 (0%)	0	4/2100 (0.2%)	4
Sudden death	6/2092 (0.3%)	6	3/2100 (0.1%)	3
Vascular stent restenosis	2/2092 (0.1%)	2	1/2100 (0%)	1
Catheter site haemorrhage	0/2092 (0%)	0	1/2100 (0%)	1
Vascular stent thrombosis	1/2092 (0%)	1	0/2100 (0%)	0
Hepatobiliary disorders
Bile duct stone	0/2092 (0%)	0	1/2100 (0%)	1
Cholangitis	1/2092 (0%)	1	1/2100 (0%)	1
Cholecystitis	7/2092 (0.3%)	7	3/2100 (0.1%)	3
Cholecystitis acute	4/2092 (0.2%)	4	4/2100 (0.2%)	4
Cholecystitis chronic	1/2092 (0%)	1	0/2100 (0%)	0
Cholelithiasis	5/2092 (0.2%)	5	3/2100 (0.1%)	3
Hepatic cirrhosis	0/2092 (0%)	0	2/2100 (0.1%)	2
Hepatorenal syndrome	1/2092 (0%)	1	0/2100 (0%)	0
Hydrocholecystis	1/2092 (0%)	1	0/2100 (0%)	0
Jaundice	1/2092 (0%)	1	0/2100 (0%)	0
Immune system disorders
Drug hypersensitivity	0/2092 (0%)	0	1/2100 (0%)	1
Hypersensitivity	1/2092 (0%)	1	1/2100 (0%)	1
Infections and infestations
Abdominal abscess	2/2092 (0.1%)	2	0/2100 (0%)	0
Abscess intestinal	1/2092 (0%)	1	0/2100 (0%)	0
Abscess limb	2/2092 (0.1%)	2	0/2100 (0%)	0
Appendicitis	1/2092 (0%)	1	2/2100 (0.1%)	2
Atypical pneumonia	1/2092 (0%)	1	1/2100 (0%)	1
Bacterial sepsis	1/2092 (0%)	1	0/2100 (0%)	0
Bronchitis	6/2092 (0.3%)	6	2/2100 (0.1%)	2
Bronchitis viral	0/2092 (0%)	0	1/2100 (0%)	1
Bronchopulmonary aspergillosis	1/2092 (0%)	1	0/2100 (0%)	0
Bronchopulmonary aspergillosis allergic	1/2092 (0%)	1	0/2100 (0%)	0
Cellulitis	11/2092 (0.5%)	11	2/2100 (0.1%)	3
Chronic hepatitis C	1/2092 (0%)	1	0/2100 (0%)	0
Cystitis	0/2092 (0%)	0	1/2100 (0%)	1
Diabetic foot infection	0/2092 (0%)	0	1/2100 (0%)	1
Diabetic gangrene	1/2092 (0%)	1	1/2100 (0%)	1
Diverticulitis	1/2092 (0%)	1	1/2100 (0%)	1
Endocarditis bacterial	0/2092 (0%)	0	1/2100 (0%)	1
Endophthalmitis	1/2092 (0%)	1	0/2100 (0%)	0
Enterococcal sepsis	1/2092 (0%)	1	0/2100 (0%)	0
Epididymitis	1/2092 (0%)	1	0/2100 (0%)	0
Erysipelas	1/2092 (0%)	1	2/2100 (0.1%)	2
Escherichia urinary tract infection	0/2092 (0%)	0	3/2100 (0.1%)	3
Febrile infection	1/2092 (0%)	1	0/2100 (0%)	0
Fungal infection	0/2092 (0%)	0	1/2100 (0%)	1
Gangrene	6/2092 (0.3%)	7	4/2100 (0.2%)	4
Gas gangrene	1/2092 (0%)	1	0/2100 (0%)	0
Gastroenteritis	3/2092 (0.1%)	4	3/2100 (0.1%)	3
Gastroenteritis viral	1/2092 (0%)	1	1/2100 (0%)	1
HIV infection	1/2092 (0%)	1	0/2100 (0%)	0
Infection	0/2092 (0%)	0	1/2100 (0%)	1
Infectious pleural effusion	2/2092 (0.1%)	2	0/2100 (0%)	0
Infective exacerbation of bronchiectasis	1/2092 (0%)	1	0/2100 (0%)	0
Infective exacerbation of chronic obstructive airways disease	1/2092 (0%)	1	0/2100 (0%)	0
Kidney infection	0/2092 (0%)	0	1/2100 (0%)	1
Klebsiella sepsis	1/2092 (0%)	1	0/2100 (0%)	0
Lower respiratory tract infection	1/2092 (0%)	1	2/2100 (0.1%)	2
Lung infection	1/2092 (0%)	1	0/2100 (0%)	0
Mediastinitis	1/2092 (0%)	1	0/2100 (0%)	0
Neuroborreliosis	1/2092 (0%)	1	0/2100 (0%)	0
Nosocomial infection	1/2092 (0%)	1	0/2100 (0%)	0
Osteomyelitis	2/2092 (0.1%)	2	1/2100 (0%)	1
Paronychia	0/2092 (0%)	0	2/2100 (0.1%)	2
Parotitis	0/2092 (0%)	0	1/2100 (0%)	1
Pelvic sepsis	1/2092 (0%)	1	0/2100 (0%)	0
Perirectal abscess	1/2092 (0%)	1	0/2100 (0%)	0
Pneumocystis jirovecii pneumonia	1/2092 (0%)	1	0/2100 (0%)	0
Pneumonia	35/2092 (1.7%)	37	31/2100 (1.5%)	31
Pneumonia respiratory syncytial viral	1/2092 (0%)	1	0/2100 (0%)	0
Pneumonia streptococcal	0/2092 (0%)	0	1/2100 (0%)	1
Pneumonia viral	0/2092 (0%)	0	1/2100 (0%)	1
Postoperative abscess	0/2092 (0%)	0	1/2100 (0%)	1
Pulmonary tuberculosis	1/2092 (0%)	1	0/2100 (0%)	0
Pyelonephritis	1/2092 (0%)	1	3/2100 (0.1%)	3
Pyelonephritis acute	1/2092 (0%)	1	1/2100 (0%)	1
Respiratory tract infection	2/2092 (0.1%)	2	0/2100 (0%)	0
Respiratory tract infection viral	0/2092 (0%)	0	1/2100 (0%)	1
Sepsis	7/2092 (0.3%)	7	5/2100 (0.2%)	5
Septic shock	3/2092 (0.1%)	3	1/2100 (0%)	1
Sinusitis	0/2092 (0%)	0	1/2100 (0%)	1
Subdural empyema	1/2092 (0%)	1	0/2100 (0%)	0
Tuberculosis	0/2092 (0%)	0	1/2100 (0%)	1
Upper respiratory tract infection	1/2092 (0%)	1	2/2100 (0.1%)	2
Urinary tract infection	4/2092 (0.2%)	4	6/2100 (0.3%)	6
Urinary tract infection bacterial	1/2092 (0%)	1	0/2100 (0%)	0
Urosepsis	0/2092 (0%)	0	1/2100 (0%)	1
Viral infection	2/2092 (0.1%)	2	1/2100 (0%)	1
Vulval abscess	0/2092 (0%)	0	1/2100 (0%)	1
Wound infection	0/2092 (0%)	0	1/2100 (0%)	1
Bacteraemia	0/2092 (0%)	0	1/2100 (0%)	1
Injury, poisoning and procedural complications
Acetabulum fracture	1/2092 (0%)	1	0/2100 (0%)	0
Alcohol poisoning	1/2092 (0%)	1	0/2100 (0%)	0
Ankle fracture	1/2092 (0%)	1	3/2100 (0.1%)	3
Avulsion fracture	0/2092 (0%)	0	1/2100 (0%)	1
Cardiac procedure complication	1/2092 (0%)	1	0/2100 (0%)	0
Cervical vertebral fracture	1/2092 (0%)	1	0/2100 (0%)	0
Chemical peritonitis	0/2092 (0%)	0	1/2100 (0%)	1
Concussion	0/2092 (0%)	0	1/2100 (0%)	1
Contusion	2/2092 (0.1%)	2	2/2100 (0.1%)	3
Coronary artery restenosis	0/2092 (0%)	0	1/2100 (0%)	1
Craniocerebral injury	0/2092 (0%)	0	1/2100 (0%)	1
Cystitis radiation	0/2092 (0%)	0	1/2100 (0%)	1
Face injury	1/2092 (0%)	1	0/2100 (0%)	0
Fall	1/2092 (0%)	1	0/2100 (0%)	0
Femoral neck fracture	1/2092 (0%)	1	0/2100 (0%)	0
Femur fracture	2/2092 (0.1%)	2	0/2100 (0%)	0
Fibula fracture	0/2092 (0%)	0	1/2100 (0%)	1
Flail chest	1/2092 (0%)	1	0/2100 (0%)	0
Foot fracture	1/2092 (0%)	1	0/2100 (0%)	0
Forearm fracture	2/2092 (0.1%)	2	0/2100 (0%)	0
Gastrointestinal anastomotic leak	0/2092 (0%)	0	1/2100 (0%)	1
Head injury	0/2092 (0%)	0	1/2100 (0%)	1
Hip fracture	0/2092 (0%)	0	1/2100 (0%)	1
Humerus fracture	2/2092 (0.1%)	2	2/2100 (0.1%)	2
Incarcerated incisional hernia	1/2092 (0%)	1	0/2100 (0%)	0
Incisional hernia	2/2092 (0.1%)	2	0/2100 (0%)	0
Jaw fracture	1/2092 (0%)	1	0/2100 (0%)	0
Joint dislocation	0/2092 (0%)	0	1/2100 (0%)	1
Limb injury	2/2092 (0.1%)	2	0/2100 (0%)	0
Lower limb fracture	0/2092 (0%)	0	2/2100 (0.1%)	2
Meniscus injury	0/2092 (0%)	0	1/2100 (0%)	1
Multiple injuries	0/2092 (0%)	0	1/2100 (0%)	1
Post procedural complication	1/2092 (0%)	1	1/2100 (0%)	1
Post procedural haemorrhage	1/2092 (0%)	1	2/2100 (0.1%)	2
Postoperative ileus	1/2092 (0%)	1	0/2100 (0%)	0
Procedural haemorrhage	1/2092 (0%)	1	0/2100 (0%)	0
Radius fracture	1/2092 (0%)	1	0/2100 (0%)	0
Rib fracture	1/2092 (0%)	1	3/2100 (0.1%)	3
Road traffic accident	3/2092 (0.1%)	3	1/2100 (0%)	1
Soft tissue injury	0/2092 (0%)	0	1/2100 (0%)	1
Spinal cord injury cervical	0/2092 (0%)	0	1/2100 (0%)	1
Stomal hernia	1/2092 (0%)	1	0/2100 (0%)	0
Subdural haematoma	2/2092 (0.1%)	2	1/2100 (0%)	1
Synovial rupture	1/2092 (0%)	1	0/2100 (0%)	0
Thermal burn	0/2092 (0%)	0	1/2100 (0%)	1
Tibia fracture	1/2092 (0%)	1	2/2100 (0.1%)	2
Toxicity to various agents	0/2092 (0%)	0	1/2100 (0%)	1
Traumatic haemorrhage	1/2092 (0%)	1	0/2100 (0%)	0
Upper limb fracture	1/2092 (0%)	1	1/2100 (0%)	1
Vascular graft occlusion	1/2092 (0%)	1	0/2100 (0%)	0
Vascular pseudoaneurysm	1/2092 (0%)	1	0/2100 (0%)	0
Wrist fracture	1/2092 (0%)	1	0/2100 (0%)	0
Procedural pneumothorax	1/2092 (0%)	1	0/2100 (0%)	0
Traumatic intracranial haemorrhage	1/2092 (0%)	1	0/2100 (0%)	0
Investigations
Blood creatinine increased	1/2092 (0%)	1	0/2100 (0%)	0
Blood glucose increased	1/2092 (0%)	1	6/2100 (0.3%)	6
Blood sodium decreased	0/2092 (0%)	0	1/2100 (0%)	1
Heart rate increased	1/2092 (0%)	1	0/2100 (0%)	0
Troponin increased	0/2092 (0%)	0	1/2100 (0%)	1
Metabolism and nutrition disorders
Dehydration	1/2092 (0%)	1	2/2100 (0.1%)	2
Diabetes mellitus	1/2092 (0%)	1	3/2100 (0.1%)	3
Diabetes mellitus inadequate control	0/2092 (0%)	0	1/2100 (0%)	1
Diabetic ketoacidosis	3/2092 (0.1%)	3	1/2100 (0%)	1
Diabetic metabolic decompensation	0/2092 (0%)	0	1/2100 (0%)	1
Fluid overload	1/2092 (0%)	1	0/2100 (0%)	0
Gout	1/2092 (0%)	1	0/2100 (0%)	0
Hyperglycaemia	5/2092 (0.2%)	5	7/2100 (0.3%)	7
Hyperkalaemia	0/2092 (0%)	0	1/2100 (0%)	1
Hypoglycaemia	3/2092 (0.1%)	4	5/2100 (0.2%)	5
Hypokalaemia	0/2092 (0%)	0	1/2100 (0%)	2
Obesity	1/2092 (0%)	1	1/2100 (0%)	1
Musculoskeletal and connective tissue disorders
Amyotrophy	1/2092 (0%)	1	0/2100 (0%)	0
Arthralgia	0/2092 (0%)	0	1/2100 (0%)	1
Back pain	2/2092 (0.1%)	2	2/2100 (0.1%)	2
Bursitis	0/2092 (0%)	0	1/2100 (0%)	1
Flank pain	0/2092 (0%)	0	1/2100 (0%)	1
Foot deformity	0/2092 (0%)	0	2/2100 (0.1%)	2
Gouty arthritis	0/2092 (0%)	0	2/2100 (0.1%)	2
Intervertebral disc disorder	0/2092 (0%)	0	1/2100 (0%)	1
Intervertebral disc protrusion	2/2092 (0.1%)	2	4/2100 (0.2%)	4
Lumbar spinal stenosis	1/2092 (0%)	1	0/2100 (0%)	0
Muscular weakness	1/2092 (0%)	1	1/2100 (0%)	1
Musculoskeletal chest pain	2/2092 (0.1%)	2	1/2100 (0%)	1
Osteitis	1/2092 (0%)	1	1/2100 (0%)	1
Osteoarthritis	14/2092 (0.7%)	15	9/2100 (0.4%)	9
Pain in extremity	0/2092 (0%)	0	1/2100 (0%)	1
Periarthritis	0/2092 (0%)	0	1/2100 (0%)	1
Rotator cuff syndrome	4/2092 (0.2%)	4	0/2100 (0%)	0
Spinal column stenosis	1/2092 (0%)	1	0/2100 (0%)	0
Spinal osteoarthritis	1/2092 (0%)	1	0/2100 (0%)	0
Spinal pain	1/2092 (0%)	1	1/2100 (0%)	1
Spondylolisthesis	0/2092 (0%)	0	1/2100 (0%)	1
Trigger finger	0/2092 (0%)	0	1/2100 (0%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/2092 (0%)	1	0/2100 (0%)	0
Adenocarcinoma of colon	0/2092 (0%)	0	1/2100 (0%)	1
Basal cell carcinoma	5/2092 (0.2%)	6	10/2100 (0.5%)	15
Benign neoplasm of eyelid	1/2092 (0%)	1	0/2100 (0%)	0
Benign renal neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Bladder cancer	2/2092 (0.1%)	2	5/2100 (0.2%)	5
Bladder cancer recurrent	0/2092 (0%)	0	1/2100 (0%)	1
Bladder neoplasm	1/2092 (0%)	1	1/2100 (0%)	1
Bladder transitional cell carcinoma	1/2092 (0%)	1	1/2100 (0%)	1
Bone cancer	0/2092 (0%)	0	1/2100 (0%)	1
Brain neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Breast cancer	1/2092 (0%)	1	0/2100 (0%)	0
Breast cancer in situ	0/2092 (0%)	0	1/2100 (0%)	1
Breast cancer metastatic	0/2092 (0%)	0	1/2100 (0%)	1
Bronchial carcinoma	1/2092 (0%)	1	0/2100 (0%)	0
Cholangiocarcinoma	1/2092 (0%)	1	0/2100 (0%)	0
Colon adenoma	0/2092 (0%)	0	1/2100 (0%)	1
Colon cancer	3/2092 (0.1%)	3	1/2100 (0%)	1
Colorectal cancer	1/2092 (0%)	1	0/2100 (0%)	0
Gastric cancer	1/2092 (0%)	1	2/2100 (0.1%)	2
Gastrooesophageal cancer	1/2092 (0%)	1	0/2100 (0%)	0
Hepatic cancer	0/2092 (0%)	0	1/2100 (0%)	1
Hepatic neoplasm	0/2092 (0%)	0	1/2100 (0%)	1
Hodgkin's disease	1/2092 (0%)	1	0/2100 (0%)	0
Intraductal proliferative breast lesion	1/2092 (0%)	1	0/2100 (0%)	0
Lung adenocarcinoma	1/2092 (0%)	1	0/2100 (0%)	0
Lung cancer metastatic	1/2092 (0%)	1	3/2100 (0.1%)	3
Lung carcinoma cell type unspecified stage IV	2/2092 (0.1%)	2	0/2100 (0%)	0
Lung neoplasm malignant	3/2092 (0.1%)	3	1/2100 (0%)	1
Lung squamous cell carcinoma stage II	1/2092 (0%)	1	0/2100 (0%)	0
Malignant melanoma	3/2092 (0.1%)	3	1/2100 (0%)	1
Meningioma	1/2092 (0%)	1	0/2100 (0%)	0
Metastases to liver	0/2092 (0%)	0	1/2100 (0%)	1
Metastatic gastric cancer	0/2092 (0%)	0	2/2100 (0.1%)	2
Neoplasm malignant	0/2092 (0%)	0	2/2100 (0.1%)	2
Neuroendocrine carcinoma	0/2092 (0%)	0	1/2100 (0%)	1
Non-Hodgkin's lymphoma	1/2092 (0%)	1	0/2100 (0%)	0
Oesophageal carcinoma	0/2092 (0%)	0	2/2100 (0.1%)	2
Pancreatic carcinoma	3/2092 (0.1%)	3	1/2100 (0%)	1
Pancreatic carcinoma metastatic	2/2092 (0.1%)	2	0/2100 (0%)	0
Pancreatic neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Parathyroid tumour benign	1/2092 (0%)	1	0/2100 (0%)	0
Plasma cell myeloma	1/2092 (0%)	1	0/2100 (0%)	0
Prostate cancer	7/2092 (0.3%)	7	4/2100 (0.2%)	4
Prostate cancer stage 0	0/2092 (0%)	0	1/2100 (0%)	1
Prostate cancer stage II	0/2092 (0%)	0	1/2100 (0%)	1
Prostatic adenoma	0/2092 (0%)	0	3/2100 (0.1%)	3
Rectal cancer	2/2092 (0.1%)	2	0/2100 (0%)	0
Renal cancer	4/2092 (0.2%)	4	2/2100 (0.1%)	2
Renal cell carcinoma	0/2092 (0%)	0	2/2100 (0.1%)	2
Small cell lung cancer	2/2092 (0.1%)	2	1/2100 (0%)	2
Small cell lung cancer metastatic	0/2092 (0%)	0	1/2100 (0%)	1
Squamous cell carcinoma	2/2092 (0.1%)	3	5/2100 (0.2%)	9
Squamous cell carcinoma of skin	0/2092 (0%)	0	2/2100 (0.1%)	2
Tonsil cancer metastatic	1/2092 (0%)	1	0/2100 (0%)	0
Transitional cell carcinoma	0/2092 (0%)	0	1/2100 (0%)	1
Urinary tract neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Vocal cord neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Benign ear neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Bowen's disease	1/2092 (0%)	1	0/2100 (0%)	0
Ear neoplasm	1/2092 (0%)	1	0/2100 (0%)	0
Nervous system disorders
Altered state of consciousness	0/2092 (0%)	0	2/2100 (0.1%)	2
Ataxia	1/2092 (0%)	1	1/2100 (0%)	1
Basal ganglia infarction	1/2092 (0%)	1	0/2100 (0%)	0
Basal ganglia stroke	0/2092 (0%)	0	1/2100 (0%)	1
Brain stem infarction	2/2092 (0.1%)	2	0/2100 (0%)	0
Carotid artery stenosis	4/2092 (0.2%)	4	7/2100 (0.3%)	7
Cauda equina syndrome	1/2092 (0%)	1	0/2100 (0%)	0
Cerebral haemorrhage	1/2092 (0%)	1	2/2100 (0.1%)	2
Cerebral infarction	4/2092 (0.2%)	4	2/2100 (0.1%)	2
Cerebral ischaemia	0/2092 (0%)	0	2/2100 (0.1%)	2
Cerebral small vessel ischaemic disease	0/2092 (0%)	0	1/2100 (0%)	1
Cerebrovascular accident	9/2092 (0.4%)	10	9/2100 (0.4%)	9
Cerebrovascular insufficiency	2/2092 (0.1%)	2	0/2100 (0%)	0
Cervical radiculopathy	0/2092 (0%)	0	1/2100 (0%)	1
Cervicobrachial syndrome	1/2092 (0%)	1	0/2100 (0%)	0
Coma	0/2092 (0%)	0	1/2100 (0%)	1
Dementia	0/2092 (0%)	0	1/2100 (0%)	1
Dementia Alzheimer's type	0/2092 (0%)	0	1/2100 (0%)	1
Diabetic neuropathy	1/2092 (0%)	1	0/2100 (0%)	0
Dizziness	0/2092 (0%)	0	2/2100 (0.1%)	2
Embolic stroke	1/2092 (0%)	1	1/2100 (0%)	1
Encephalopathy	0/2092 (0%)	0	2/2100 (0.1%)	2
Epilepsy	1/2092 (0%)	1	0/2100 (0%)	0
Facial paralysis	1/2092 (0%)	1	0/2100 (0%)	0
Haemorrhagic stroke	1/2092 (0%)	1	2/2100 (0.1%)	2
Headache	1/2092 (0%)	1	1/2100 (0%)	1
Hypertensive encephalopathy	0/2092 (0%)	0	1/2100 (0%)	1
IIIrd nerve paralysis	1/2092 (0%)	1	0/2100 (0%)	0
Intracranial aneurysm	1/2092 (0%)	1	0/2100 (0%)	0
Ischaemic stroke	11/2092 (0.5%)	11	17/2100 (0.8%)	17
Lacunar infarction	2/2092 (0.1%)	2	0/2100 (0%)	0
Loss of consciousness	1/2092 (0%)	1	1/2100 (0%)	1
Lumbar radiculopathy	0/2092 (0%)	0	1/2100 (0%)	1
Meralgia paraesthetica	1/2092 (0%)	1	0/2100 (0%)	0
Migraine	1/2092 (0%)	1	0/2100 (0%)	0
Monoparesis	0/2092 (0%)	0	1/2100 (0%)	1
Myelitis transverse	0/2092 (0%)	0	1/2100 (0%)	1
Nerve root compression	1/2092 (0%)	1	0/2100 (0%)	0
Parkinson's disease	1/2092 (0%)	1	0/2100 (0%)	0
Presyncope	0/2092 (0%)	0	2/2100 (0.1%)	2
Radiculopathy	0/2092 (0%)	0	1/2100 (0%)	1
Syncope	7/2092 (0.3%)	8	2/2100 (0.1%)	4
Thalamic infarction	1/2092 (0%)	1	0/2100 (0%)	0
Toxic encephalopathy	1/2092 (0%)	1	0/2100 (0%)	0
Transient ischaemic attack	11/2092 (0.5%)	11	11/2100 (0.5%)	11
VIth nerve paralysis	0/2092 (0%)	0	2/2100 (0.1%)	2
Vascular dementia	0/2092 (0%)	0	1/2100 (0%)	1
Vertebrobasilar insufficiency	0/2092 (0%)	0	2/2100 (0.1%)	2
Cerebellar infarction	1/2092 (0%)	1	0/2100 (0%)	0
Product Issues
Device breakage	0/2092 (0%)	0	1/2100 (0%)	1
Device malfunction	0/2092 (0%)	0	1/2100 (0%)	1
Psychiatric disorders
Abnormal behaviour	0/2092 (0%)	0	1/2100 (0%)	1
Acute stress disorder	0/2092 (0%)	0	1/2100 (0%)	1
Alcoholism	0/2092 (0%)	0	1/2100 (0%)	1
Confusional state	0/2092 (0%)	0	1/2100 (0%)	1
Depression	2/2092 (0.1%)	2	3/2100 (0.1%)	3
Major depression	0/2092 (0%)	0	2/2100 (0.1%)	2
Mental disorder	0/2092 (0%)	0	1/2100 (0%)	1
Panic attack	0/2092 (0%)	0	1/2100 (0%)	1
Schizophrenia	1/2092 (0%)	3	0/2100 (0%)	0
Somatic symptom disorder	0/2092 (0%)	0	1/2100 (0%)	1
Stress	0/2092 (0%)	0	1/2100 (0%)	1
Substance-induced mood disorder	0/2092 (0%)	0	1/2100 (0%)	1
Suicide attempt	0/2092 (0%)	0	1/2100 (0%)	1
Renal and urinary disorders
Acute kidney injury	11/2092 (0.5%)	11	6/2100 (0.3%)	6
Calculus urethral	1/2092 (0%)	1	0/2100 (0%)	0
Calculus urinary	2/2092 (0.1%)	2	0/2100 (0%)	0
Chronic kidney disease	2/2092 (0.1%)	2	0/2100 (0%)	0
Dysuria	1/2092 (0%)	1	0/2100 (0%)	0
Haematuria	0/2092 (0%)	0	1/2100 (0%)	1
Haemorrhage urinary tract	0/2092 (0%)	0	1/2100 (0%)	1
Nephrolithiasis	5/2092 (0.2%)	5	2/2100 (0.1%)	2
Renal colic	1/2092 (0%)	1	0/2100 (0%)	0
Renal failure	1/2092 (0%)	1	1/2100 (0%)	1
Stag horn calculus	1/2092 (0%)	1	0/2100 (0%)	0
Ureteric stenosis	1/2092 (0%)	1	0/2100 (0%)	0
Ureterolithiasis	2/2092 (0.1%)	2	0/2100 (0%)	0
Urethral stenosis	1/2092 (0%)	1	1/2100 (0%)	1
Urinary incontinence	0/2092 (0%)	0	1/2100 (0%)	1
Urinary retention	1/2092 (0%)	1	1/2100 (0%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/2092 (0.1%)	2	1/2100 (0%)	1
Breast fibrosis	1/2092 (0%)	1	0/2100 (0%)	0
Genital prolapse	0/2092 (0%)	0	1/2100 (0%)	1
Ovarian cyst	1/2092 (0%)	1	0/2100 (0%)	0
Prostatic dysplasia	1/2092 (0%)	1	0/2100 (0%)	0
Prostatitis	1/2092 (0%)	1	0/2100 (0%)	0
Uterine haemorrhage	1/2092 (0%)	1	0/2100 (0%)	0
Uterine prolapse	1/2092 (0%)	1	0/2100 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	2/2092 (0.1%)	2	2/2100 (0.1%)	2
Acute respiratory failure	6/2092 (0.3%)	6	1/2100 (0%)	1
Asthma	2/2092 (0.1%)	2	1/2100 (0%)	1
Chronic obstructive pulmonary disease	7/2092 (0.3%)	9	5/2100 (0.2%)	6
Dyspnoea	1/2092 (0%)	1	5/2100 (0.2%)	5
Dyspnoea exertional	1/2092 (0%)	1	1/2100 (0%)	1
Epistaxis	1/2092 (0%)	1	1/2100 (0%)	1
Hypoxia	0/2092 (0%)	0	1/2100 (0%)	1
Pleural effusion	3/2092 (0.1%)	3	1/2100 (0%)	1
Pleurisy	1/2092 (0%)	1	0/2100 (0%)	0
Pneumonia aspiration	1/2092 (0%)	1	2/2100 (0.1%)	2
Pneumothorax	2/2092 (0.1%)	2	0/2100 (0%)	0
Pulmonary embolism	1/2092 (0%)	1	3/2100 (0.1%)	3
Pulmonary mass	1/2092 (0%)	1	0/2100 (0%)	0
Pulmonary oedema	3/2092 (0.1%)	3	3/2100 (0.1%)	3
Respiratory failure	2/2092 (0.1%)	2	0/2100 (0%)	0
Sleep apnoea syndrome	0/2092 (0%)	0	1/2100 (0%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/2092 (0%)	0	1/2100 (0%)	1
Dermatosis	1/2092 (0%)	1	0/2100 (0%)	0
Diabetic foot	1/2092 (0%)	1	3/2100 (0.1%)	4
Eczema	1/2092 (0%)	1	0/2100 (0%)	0
Skin lesion	0/2092 (0%)	0	1/2100 (0%)	1
Skin ulcer	6/2092 (0.3%)	6	0/2100 (0%)	0
Vascular disorders
Aortic aneurysm	2/2092 (0.1%)	2	1/2100 (0%)	1
Aortic stenosis	1/2092 (0%)	1	2/2100 (0.1%)	2
Arterial occlusive disease	0/2092 (0%)	0	1/2100 (0%)	1
Circulatory collapse	0/2092 (0%)	0	1/2100 (0%)	1
Deep vein thrombosis	2/2092 (0.1%)	2	3/2100 (0.1%)	4
Dry gangrene	2/2092 (0.1%)	2	0/2100 (0%)	0
Extremity necrosis	2/2092 (0.1%)	2	2/2100 (0.1%)	2
Haematoma	0/2092 (0%)	0	1/2100 (0%)	1
Hypertension	7/2092 (0.3%)	7	8/2100 (0.4%)	8
Hypertensive crisis	2/2092 (0.1%)	2	3/2100 (0.1%)	3
Hypertensive emergency	1/2092 (0%)	1	0/2100 (0%)	0
Hypotension	0/2092 (0%)	0	1/2100 (0%)	1
Iliac artery occlusion	1/2092 (0%)	1	0/2100 (0%)	0
Intermittent claudication	1/2092 (0%)	1	0/2100 (0%)	0
Orthostatic hypotension	1/2092 (0%)	1	0/2100 (0%)	0
Peripheral arterial occlusive disease	14/2092 (0.7%)	17	10/2100 (0.5%)	11
Peripheral artery occlusion	0/2092 (0%)	0	1/2100 (0%)	1
Peripheral artery stenosis	3/2092 (0.1%)	3	2/2100 (0.1%)	2
Peripheral artery thrombosis	0/2092 (0%)	0	1/2100 (0%)	1
Peripheral ischaemia	1/2092 (0%)	2	4/2100 (0.2%)	4
Peripheral vascular disorder	4/2092 (0.2%)	4	1/2100 (0%)	1
Other (Not Including Serious) Adverse Events
	Omarigliptin 25 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	788/2092 (37.7%)		794/2100 (37.8%)
Infections and infestations
Nasopharyngitis	123/2092 (5.9%)	167	145/2100 (6.9%)	195
Upper respiratory tract infection	123/2092 (5.9%)	163	120/2100 (5.7%)	150
Urinary tract infection	108/2092 (5.2%)	131	98/2100 (4.7%)	141
Investigations
Blood glucose increased	97/2092 (4.6%)	139	139/2100 (6.6%)	199
Metabolism and nutrition disorders
Hypoglycaemia	530/2092 (25.3%)	3990	473/2100 (22.5%)	3688

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.