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TECOS: Sitagliptin Cardiovascular Outcomes Study (MK-0431-082)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00790205
Collaborator
Duke Clinical Research Institute, Oxford Diabetes Trials Unit (Other)
14,671
Enrollment
2
Arms
75.6
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This is a clinical trial designed to assess the cardiovascular outcome of long-term treatment with sitagliptin used as part of usual care compared to usual care without sitagliptin in participants with type 2 diabetes mellitus (T2DM) having a history of cardiovascular (CV) disease and a hemoglobin A1c (HbA1c) of 6.5% to 8.0%.

Primary hypothesis A is that sitagliptin, when used as part of usual care, is non-inferior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint of Major Adverse Cardiovascular Event (MACE) plus. If hypothesis A is satisfied: hypothesis B is that sitagliptin, when used as part of usual care, is superior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
14671 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
TECOS: A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Sitagliptin in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Actual Study Start Date :
Dec 10, 2008
Actual Primary Completion Date :
Mar 30, 2015
Actual Study Completion Date :
Mar 30, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sitagliptin

Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.

Drug: Sitagliptin
Sitagliptin, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily.
Other Names:
  • MK-0431
  • Januvia®

    		•
    Placebo Comparator: Placebo

    Placebo to sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.

    Drug: Placebo
    Placebo tablet matching the 50 mg or 100 mg sitagliptin tablet, orally, once daily.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population) [Up to 5 years]

      Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

    2. Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population) [Up to 5 years]

      Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

    Secondary Outcome Measures

    1. Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population) [Up to 5 years]

      CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.

    2. Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population) [Up to 5 years]

      CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.

    3. Percent Incidence of All-cause Mortality (Per Protocol Population) [Up to 5 years]

      Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.

    4. Percent Incidence of All-cause Mortality (Intent to Treat Population) [Up to 5 years]

      Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.

    5. Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population) [Up to 5 years]

      Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.

    6. Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population) [Up to 5 years]

      Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.

    7. Change From Baseline in Renal Function Over Time (Per Protocol Population) [Baseline and up to 5 years]

      Change in renal function based on estimated glomerular filtration rate [eGFR] using the Modification of Diet in Renal Disease [MDRD] method.

    8. Change From Baseline in Renal Function Over Time (Intent to Treat Population) [Baseline and up to 5 years]

      Change in renal function based on eGFR using the MDRD method.

    9. Change From Baseline in HbA1c Over Time (Per Protocol Population) [Baseline and up to 4 years]

      HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.

    10. Change From Baseline in HbA1c Over Time (Intent to Treat Population) [Baseline and up to 4 years]

      HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.

    11. Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) [Baseline and up to 5 years]

      Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.

    12. Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) [Baseline and up to 5 years]

      Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.

    13. Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population) [Up to 5 years]

      Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.

    14. Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population) [Up to 5 years]

      Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.

    15. Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population) [Up to 5 years]

      In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent [AHA] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)

    16. Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population) [Up to 5 years]

      In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Has T2DM

    • Has HbA1c between 6.5% (48 mmol/mol) and 8.0% (64 mmol/mol) on stable dose(s) of antihyperglycemic agent(s), including insulin

    • Has pre-existing cardiovascular disease

    Exclusion Criteria:

    • Has a history of type 1 diabetes mellitus or ketoacidosis.

    • Is not able to take sitagliptin

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC
    • Duke Clinical Research Institute, Oxford Diabetes Trials Unit

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00790205
    Other Study ID Numbers:
    • 0431-082
    • 2008_523
    • 2008-006719-20
    First Posted:
    Nov 13, 2008
    Last Update Posted:
    Nov 23, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Sitagliptin Phosphate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 14,671 participants were randomized to treatment, provided consent and did not have any Good Clinical Practice (GCP) deviations.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Period Title: Overall Study
    STARTED 7332 7339
    Treated 7266 7274
    COMPLETED 6972 6905
    NOT COMPLETED 360 434

    Baseline Characteristics

    Arm/Group Title Sitagliptin Placebo Total
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years Total of all reporting groups
    Overall Participants 7332 7339 14671
    Age, Customized (Number) [Number]
    Adults 18 - 64 years
    3315
    (7.9) 45.2%
    3301
    (8.0) 45%
    65.5
    (8.0) 0.4%
    From 65 - 84 years
    3813
    52%
    3821
    52.1%
    7634
    52%
    85 years and over
    46
    0.6%
    55
    0.7%
    101
    0.7%
    Unknown age
    158
    2.2%
    162
    2.2%
    320
    2.2%
    Sex: Female, Male (Count of Participants)
    Female
    2134
    29.1%
    2163
    29.5%
    4297
    29.3%
    Male
    5198
    70.9%
    5176
    70.5%
    10374
    70.7%
    Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL/min/1.73 m^2]
    74.9
    (21.3)
    74.9
    (20.9)
    74.9
    (21.1)
    Hemoglobin A1c (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percentage of HbA1c]
    7.2
    (0.5)
    7.2
    (0.5)
    7.2
    (0.5)
    Urine albumin creatinine ratio (g/mol Creatinine) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/mol Creatinine]
    8.6
    (37.4)
    8.4
    (36.0)
    8.5
    (36.7)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)
    Description Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7257 7266
    Number [Percentage of participants]
    9.6
    0.1%
    9.6
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Hazard Ratio of Sitagliptin/Placebo: the between-treatment difference in time to the first primary composite CV outcome measure was assessed by the hazard ratio between the sitagliptin and placebo groups. The confidence interval for the hazard ratio was computed and compared to 1.30, the non-inferiority margin.
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.88 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)
    Description Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7332 7339
    Number [Percentage of participants]
    11.4
    0.2%
    11.6
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Hazard Ratio of Sitagliptin/Placebo: the between-treatment difference in time to the first primary composite CV outcome measure was assessed by the hazard ratio between the sitagliptin and placebo groups. The confidence interval for the hazard ratio was computed and compared to 1.30, the non-inferiority margin.
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.89 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)
    Description CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7257 7266
    Number [Percentage of participants]
    8.4
    0.1%
    8.3
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Hazard Ratio of Sitagliptin/Placebo: the between-treatment difference in time to the first primary composite CV outcome measure was assessed by the hazard ratio between the sitagliptin and placebo groups. The confidence interval for the hazard ratio was computed and compared to 1.30, the non-inferiority margin.
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.89 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)
    Description CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7332 7339
    Number [Percentage of participants]
    10.2
    0.1%
    10.2
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments Hazard Ratio of Sitagliptin/Placebo: the between-treatment difference in time to the first primary composite CV outcome measure was assessed by the hazard ratio between the sitagliptin and placebo groups. The confidence interval for the hazard ratio was computed and compared to 1.30, the non-inferiority margin.
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.89 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percent Incidence of All-cause Mortality (Per Protocol Population)
    Description Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7257 7266
    Number [Percentage of participants]
    4.7
    0.1%
    4.3
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in mortality due to all causes was assessed by the hazard ratio between the Sitagliptin and Placebo groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.435
    Comments
    Method Cox proportional hazards model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.91 to 1.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percent Incidence of All-cause Mortality (Intent to Treat Population)
    Description Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7332 7339
    Number [Percentage of participants]
    7.5
    0.1%
    7.3
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in mortality due to all causes was assessed by the hazard ratio between the Sitagliptin and Placebo groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.875
    Comments
    Method Cox proportional hazards model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.90 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)
    Description Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7257 7266
    Number [Percentage of participants]
    2.8
    0%
    2.8
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in CHF cases requiring hospitalization was assessed by the hazard ratio between the Sitagliptin and Placebo groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.858
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group and history of CHF at baseline as explanatory variables.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.81 to 1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)
    Description Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7332 7339
    Number [Percentage of participants]
    3.1
    0%
    3.1
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments Hazard Ratio of Sitagliptin/Placebo: The between-treatment difference in CHF cases requiring hospitalization was assessed by the hazard ratio between the Sitagliptin and Placebo groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.983
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group and history of CHF at baseline as explanatory variables.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.83 to 1.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in Renal Function Over Time (Per Protocol Population)
    Description Change in renal function based on estimated glomerular filtration rate [eGFR] using the Modification of Diet in Renal Disease [MDRD] method.
    Time Frame Baseline and up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data. Number of participants analyzed consists of those participants with a baseline value.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7182 7203
    Month 4; Sitagliptin, n= 3859; Placebo, n= 3864
    -1.9
    (14.2)
    -0.8
    (14.3)
    Month 8; Sitagliptin, n= 3562; Placebo, n= 3501
    -2.5
    (14.9)
    -0.9
    (15.1)
    Month 12; Sitagliptin, n=4912, Placebo, n=4778
    -1.8
    (15.8)
    -0.5
    (16.2)
    Month 24; Sitagliptin, n=4782, Placebo, n=4637
    -3.1
    (17.9)
    -1.7
    (17.5)
    Month 36; Sitagliptin, n=2776, Placebo, n=2614
    -3.7
    (18.0)
    -1.6
    (18.8)
    Month 48; Sitagliptin, n=1096, Placebo, n=1056
    -3.7
    (18.3)
    -2.8
    (18.4)
    Month 60; Sitagliptin, n=79, Placebo, n=88
    -3.5
    (18.2)
    -6.4
    (17.3)
    10. Secondary Outcome
    Title Change From Baseline in Renal Function Over Time (Intent to Treat Population)
    Description Change in renal function based on eGFR using the MDRD method.
    Time Frame Baseline and up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation. Number of participants analyzed consists of those participants with a baseline value.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7254 7274
    Month 4; Sitagliptin, n=3949; Placebo, n=3977
    -1.8
    (14.3)
    -0.8
    (14.3)
    Month 8; Sitagliptin, n=3687; Placebo, n=3648
    -2.4
    (14.8)
    -0.9
    (15.2)
    Month 12; Sitagliptin, n=5082; Placebo, n=5015
    -1.8
    (15.8)
    -0.5
    (16.3)
    Month 24; Sitagliptin, n=5157; Placebo, n=5071
    -3.2
    (17.9)
    -1.7
    (17.7)
    Month 36; Sitagliptin, n=3037; Placebo, n=2942
    -3.8
    (18.1)
    -1.6
    (18.7)
    Month 48; Sitagliptin, n=1237; Placebo, n=1210
    -4.0
    (18.4)
    -2.8
    (18.3)
    Month 60; Sitagliptin, n=93; Placebo, n=106
    -4.2
    (17.4)
    -5.7
    (17.2)
    11. Secondary Outcome
    Title Change From Baseline in HbA1c Over Time (Per Protocol Population)
    Description HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.
    Time Frame Baseline and up to 4 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data. Number of participants analyzed consists of those participants with a baseline value.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7250 7258
    Month 4; Sitagliptin, n=6632, Placebo, n=6588
    -0.3
    (0.8)
    0.1
    (0.9)
    Month 8; Sitagliptin, n=6294, Placebo, n=6197
    -0.3
    (0.9)
    0.1
    (1.0)
    Month 12; Sitagliptin, n=6217, Placebo, n=6092
    -0.2
    (1.0)
    0.1
    (1.0)
    Month 24; Sitagliptin, n=5668, Placebo, n=5475
    -0.1
    (1.0)
    0.2
    (1.1)
    Month 36; Sitagliptin, n=3227, Placebo, n=3083
    -0.1
    (1.1)
    0.1
    (1.1)
    Month 48; Sitagliptin, n=1271, Placebo, n=1224
    0.0
    (1.1)
    0.1
    (1.2)
    Month 60; Sitagliptin, n=106, Placebo, n=108
    -0.1
    (1.0)
    0.0
    (0.9)
    12. Secondary Outcome
    Title Change From Baseline in HbA1c Over Time (Intent to Treat Population)
    Description HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.
    Time Frame Baseline and up to 4 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation. Number of participants analyzed consists of those participants in the intent to treat population with a baseline value.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7325 7331
    Month 4: Sitagliptin, n= 6772; Placebo, n= 6738
    -0.3
    (0.8)
    0.1
    (0.9)
    Month 8: Sitagliptin, n= 6478; Placebo, n= 6414
    -0.2
    (0.9)
    0.1
    (1.0)
    Month 12: Sitagliptin, n= 6448; Placebo, n= 6384
    -0.2
    (1.0)
    0.1
    (1.0)
    Month 24: Sitagliptin, n= 6105; Placebo, n= 5975
    -0.1
    (1.0)
    0.1
    (1.1)
    Month 36: Sitagliptin, n= 3521; Placebo, n= 3439
    -0.1
    (1.1)
    0.1
    (1.1)
    Month 48: Sitagliptin, n= 1432; Placebo, n= 1383
    0.0
    (1.1)
    0.1
    (1.2)
    Month 60: Sitagliptin, n= 123; Placebo, n= 128
    0.0
    (1.0)
    0.0
    (1.0)
    13. Secondary Outcome
    Title Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population)
    Description Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.
    Time Frame Baseline and up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data. Number of participants analyzed consists of those participants with a baseline value.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 2590 2522
    Month 4; Sitagliptin, n=664; Placebo, n=688
    -2.2
    (27.7)
    -1.4
    (24.6)
    Month 8; Sitagliptin, n=635; Placebo, n=597
    1.7
    (38.5)
    0.2
    (45.3)
    Month 12; Sitagliptin, n=1126; Placebo, n=1059
    0.8
    (27.7)
    1.2
    (33.1)
    Month 24; Sitagliptin, n=930; Placebo, n=892
    0.7
    (34.0)
    3.2
    (31.6)
    Month 36; Sitagliptin, n=488; Placebo, n=513
    2.5
    (24.0)
    4.0
    (31.0)
    Month 48; Sitagliptin, n=238; Placebo, n=233
    1.3
    (15.2)
    1.5
    (25.5)
    Month 60; Sitagliptin, n=13; Placebo, n=17
    -2.7
    (10.1)
    4.8
    (15.4)
    14. Secondary Outcome
    Title Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population)
    Description Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.
    Time Frame Baseline and up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation. Number of participants analyzed consists of those participants in the intent to treat population with a baseline value for the outcome measure.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 2606 2542
    Month 4; n=677, n=713
    -2.1
    (27.5)
    -1.4
    (24.1)
    Month 8; n=658, n=624
    2.1
    (39.4)
    0.5
    (44.5)
    Month 12; n=1167, n=1115
    1.3
    (30.2)
    1.2
    (32.3)
    Month 24; n=1011, n=964
    0.5
    (33.1)
    3.1
    (30.7)
    Month 36; n=537, n=553
    2.6
    (25.8)
    3.9
    (30.3)
    Month 48; n=265, n=256
    1.9
    (16.3)
    1.6
    (24.5)
    Month 60; n=14, n=18
    -2.5
    (9.7)
    6.4
    (16.4)
    15. Secondary Outcome
    Title Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)
    Description Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 5554 5601
    Number [Percentage of participants]
    8.6
    0.1%
    11.9
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.61 to 0.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)
    Description Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 5608 5655
    Number [Percentage of participants]
    9.7
    0.1%
    13.2
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.63 to 0.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)
    Description In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent [AHA] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Per protocol population included all randomized participants who received study medication except those participants who did not contribute at least 1 day of data to the study analysis due to a major protocol violation that excluded all of their data.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7257 7266
    Number [Percentage of participants]
    18.9
    0.3%
    24.5
    0.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.65 to 0.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)
    Description In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    Measure Participants 7332 7339
    Number [Percentage of participants]
    21.7
    0.3%
    27.9
    0.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sitagliptin, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Cox proportional hazards model
    Comments Model stratified by region with treatment group only as explanatory variable.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.68 to 0.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Up to 68 months (including up to 28 days after last dose of study drug)
    Adverse Event Reporting Description All participants as treated (APaT) population includes participants who received at least one dose of study drug.
    Arm/Group Title Sitagliptin Placebo
    Arm/Group Description Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
    All Cause Mortality
    Sitagliptin Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sitagliptin Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 928/7266 (12.8%) 909/7274 (12.5%)
    Blood and lymphatic system disorders
    Anaemia 23/7266 (0.3%) 24 23/7274 (0.3%) 23
    Anaemia vitamin B12 deficiency 1/7266 (0%) 1 0/7274 (0%) 0
    Autoimmune haemolytic anaemia 0/7266 (0%) 0 1/7274 (0%) 1
    Haemolytic anaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Haemorrhagic anaemia 0/7266 (0%) 0 1/7274 (0%) 1
    Iron deficiency anaemia 6/7266 (0.1%) 6 6/7274 (0.1%) 6
    Lymphadenopathy mediastinal 1/7266 (0%) 1 0/7274 (0%) 0
    Microcytic anaemia 1/7266 (0%) 1 1/7274 (0%) 1
    Neutropenia 1/7266 (0%) 1 0/7274 (0%) 0
    Normochromic normocytic anaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Pernicious anaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Thrombocytopenia 1/7266 (0%) 1 1/7274 (0%) 1
    Cardiac disorders
    Angina pectoris 1/7266 (0%) 1 0/7274 (0%) 0
    Atrioventricular block 0/7266 (0%) 0 1/7274 (0%) 1
    Bradycardia 1/7266 (0%) 1 0/7274 (0%) 0
    Cor pulmonale 0/7266 (0%) 0 1/7274 (0%) 1
    Coronary artery thrombosis 0/7266 (0%) 0 1/7274 (0%) 1
    Palpitations 1/7266 (0%) 1 1/7274 (0%) 1
    Pericardial effusion 0/7266 (0%) 0 1/7274 (0%) 1
    Sinus arrhythmia 1/7266 (0%) 1 0/7274 (0%) 0
    Congenital, familial and genetic disorders
    Arteriovenous malformation 0/7266 (0%) 0 1/7274 (0%) 1
    Hamartoma 0/7266 (0%) 0 1/7274 (0%) 1
    Hydrocele 2/7266 (0%) 2 1/7274 (0%) 1
    Phimosis 1/7266 (0%) 1 0/7274 (0%) 0
    Pyloric stenosis 0/7266 (0%) 0 2/7274 (0%) 2
    Syringomyelia 0/7266 (0%) 0 2/7274 (0%) 2
    Vitello-intestinal duct remnant 1/7266 (0%) 1 0/7274 (0%) 0
    Ear and labyrinth disorders
    Deafness bilateral 1/7266 (0%) 1 0/7274 (0%) 0
    Hypoacusis 0/7266 (0%) 0 1/7274 (0%) 1
    Meniere's disease 0/7266 (0%) 0 1/7274 (0%) 1
    Sudden hearing loss 1/7266 (0%) 1 0/7274 (0%) 0
    Tinnitus 1/7266 (0%) 1 1/7274 (0%) 1
    Vertigo 4/7266 (0.1%) 4 2/7274 (0%) 2
    Vertigo labyrinthine 0/7266 (0%) 0 1/7274 (0%) 1
    Vertigo positional 3/7266 (0%) 3 2/7274 (0%) 2
    Vestibular disorder 1/7266 (0%) 1 1/7274 (0%) 1
    Endocrine disorders
    Adrenocortical insufficiency acute 1/7266 (0%) 1 0/7274 (0%) 0
    Goitre 2/7266 (0%) 2 0/7274 (0%) 0
    Hyperthyroidism 0/7266 (0%) 0 1/7274 (0%) 1
    Hypothyroidism 1/7266 (0%) 1 1/7274 (0%) 1
    Inappropriate antidiuretic hormone secretion 1/7266 (0%) 1 1/7274 (0%) 1
    Eye disorders
    Amaurosis fugax 0/7266 (0%) 0 1/7274 (0%) 1
    Angle closure glaucoma 2/7266 (0%) 2 0/7274 (0%) 0
    Cataract 1/7266 (0%) 1 0/7274 (0%) 0
    Corneal degeneration 1/7266 (0%) 1 0/7274 (0%) 0
    Dacryostenosis acquired 1/7266 (0%) 1 0/7274 (0%) 0
    Optic ischaemic neuropathy 1/7266 (0%) 1 0/7274 (0%) 0
    Retinal detachment 1/7266 (0%) 2 0/7274 (0%) 0
    Visual acuity reduced 1/7266 (0%) 1 0/7274 (0%) 0
    Vitreous haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Gastrointestinal disorders
    Abdominal discomfort 0/7266 (0%) 0 1/7274 (0%) 1
    Abdominal hernia 2/7266 (0%) 2 1/7274 (0%) 1
    Abdominal hernia obstructive 0/7266 (0%) 0 1/7274 (0%) 1
    Abdominal pain 1/7266 (0%) 1 0/7274 (0%) 0
    Abdominal pain upper 4/7266 (0.1%) 4 0/7274 (0%) 0
    Abdominal wall haematoma 1/7266 (0%) 1 0/7274 (0%) 0
    Abnormal faeces 0/7266 (0%) 0 1/7274 (0%) 1
    Anal fissure 1/7266 (0%) 1 0/7274 (0%) 0
    Anal fistula 1/7266 (0%) 1 1/7274 (0%) 1
    Ascites 0/7266 (0%) 0 1/7274 (0%) 1
    Change of bowel habit 1/7266 (0%) 1 0/7274 (0%) 0
    Colitis 2/7266 (0%) 2 1/7274 (0%) 1
    Colitis ischaemic 1/7266 (0%) 1 2/7274 (0%) 2
    Colonic fistula 1/7266 (0%) 1 0/7274 (0%) 0
    Colonic pseudo-obstruction 1/7266 (0%) 1 0/7274 (0%) 0
    Constipation 4/7266 (0.1%) 4 1/7274 (0%) 1
    Crohn's disease 0/7266 (0%) 0 1/7274 (0%) 1
    Diaphragmatic hernia 1/7266 (0%) 1 1/7274 (0%) 1
    Diverticular perforation 1/7266 (0%) 1 1/7274 (0%) 1
    Diverticulum 1/7266 (0%) 1 1/7274 (0%) 1
    Diverticulum intestinal 1/7266 (0%) 1 1/7274 (0%) 1
    Diverticulum intestinal haemorrhagic 1/7266 (0%) 1 1/7274 (0%) 2
    Duodenal polyp 1/7266 (0%) 1 0/7274 (0%) 0
    Duodenal ulcer 5/7266 (0.1%) 5 3/7274 (0%) 3
    Duodenal ulcer haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Duodenitis 1/7266 (0%) 1 1/7274 (0%) 1
    Dyspepsia 1/7266 (0%) 1 0/7274 (0%) 0
    Dysphagia 1/7266 (0%) 1 1/7274 (0%) 1
    Enterovesical fistula 0/7266 (0%) 0 1/7274 (0%) 1
    Erosive oesophagitis 0/7266 (0%) 0 1/7274 (0%) 1
    Faecaloma 0/7266 (0%) 0 2/7274 (0%) 2
    Gastric polyps 1/7266 (0%) 1 0/7274 (0%) 0
    Gastric ulcer 3/7266 (0%) 3 4/7274 (0.1%) 4
    Gastric ulcer haemorrhage 2/7266 (0%) 2 2/7274 (0%) 2
    Gastritis 10/7266 (0.1%) 10 2/7274 (0%) 2
    Gastritis erosive 0/7266 (0%) 0 4/7274 (0.1%) 4
    Gastritis haemorrhagic 1/7266 (0%) 1 1/7274 (0%) 1
    Gastroduodenal ulcer 1/7266 (0%) 1 0/7274 (0%) 0
    Gastroduodenitis haemorrhagic 1/7266 (0%) 1 0/7274 (0%) 0
    Gastrointestinal haemorrhage 11/7266 (0.2%) 11 12/7274 (0.2%) 14
    Gastrointestinal necrosis 1/7266 (0%) 1 1/7274 (0%) 1
    Gastrointestinal ulcer 0/7266 (0%) 0 1/7274 (0%) 1
    Gastrointestinal ulcer haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Gastrooesophageal reflux disease 9/7266 (0.1%) 10 0/7274 (0%) 0
    Haematochezia 1/7266 (0%) 1 0/7274 (0%) 0
    Haemorrhoids 4/7266 (0.1%) 4 5/7274 (0.1%) 5
    Ileus 2/7266 (0%) 2 0/7274 (0%) 0
    Ileus paralytic 0/7266 (0%) 0 1/7274 (0%) 1
    Inguinal hernia 12/7266 (0.2%) 12 11/7274 (0.2%) 12
    Inguinal hernia, obstructive 1/7266 (0%) 1 0/7274 (0%) 0
    Intestinal haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Intestinal ischaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Intestinal obstruction 1/7266 (0%) 1 2/7274 (0%) 2
    Intestinal perforation 0/7266 (0%) 0 1/7274 (0%) 1
    Intestinal polyp 1/7266 (0%) 1 2/7274 (0%) 2
    Intussusception 0/7266 (0%) 0 1/7274 (0%) 1
    Jejunal perforation 0/7266 (0%) 0 1/7274 (0%) 1
    Large intestinal stenosis 0/7266 (0%) 0 2/7274 (0%) 2
    Large intestine perforation 1/7266 (0%) 1 0/7274 (0%) 0
    Large intestine polyp 6/7266 (0.1%) 6 2/7274 (0%) 2
    Lower gastrointestinal haemorrhage 2/7266 (0%) 2 2/7274 (0%) 2
    Mallory-Weiss syndrome 2/7266 (0%) 2 1/7274 (0%) 1
    Melaena 2/7266 (0%) 2 0/7274 (0%) 0
    Obstruction gastric 1/7266 (0%) 1 0/7274 (0%) 0
    Oedema mouth 1/7266 (0%) 1 0/7274 (0%) 0
    Oesophageal achalasia 0/7266 (0%) 0 2/7274 (0%) 2
    Oesophageal food impaction 1/7266 (0%) 1 0/7274 (0%) 0
    Oesophageal motility disorder 0/7266 (0%) 0 1/7274 (0%) 1
    Oesophageal spasm 0/7266 (0%) 0 1/7274 (0%) 1
    Oesophageal varices haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Pancreatic pseudocyst 0/7266 (0%) 0 1/7274 (0%) 1
    Peptic ulcer 2/7266 (0%) 2 0/7274 (0%) 0
    Peptic ulcer perforation 2/7266 (0%) 2 0/7274 (0%) 0
    Periodontal disease 0/7266 (0%) 0 1/7274 (0%) 1
    Pharyngo-oesophageal diverticulum 0/7266 (0%) 0 1/7274 (0%) 1
    Rectal haemorrhage 1/7266 (0%) 1 3/7274 (0%) 3
    Rectal polyp 0/7266 (0%) 0 3/7274 (0%) 3
    Rectal prolapse 1/7266 (0%) 1 0/7274 (0%) 0
    Salivary gland calculus 1/7266 (0%) 1 0/7274 (0%) 0
    Small intestinal haemorrhage 1/7266 (0%) 1 0/7274 (0%) 0
    Small intestinal obstruction 8/7266 (0.1%) 8 6/7274 (0.1%) 8
    Small intestinal perforation 1/7266 (0%) 2 0/7274 (0%) 0
    Small intestinal ulcer haemorrhage 1/7266 (0%) 1 0/7274 (0%) 0
    Tongue disorder 1/7266 (0%) 1 0/7274 (0%) 0
    Umbilical hernia 4/7266 (0.1%) 4 2/7274 (0%) 2
    Upper gastrointestinal haemorrhage 3/7266 (0%) 3 6/7274 (0.1%) 6
    Varices oesophageal 1/7266 (0%) 2 0/7274 (0%) 0
    Volvulus 0/7266 (0%) 0 1/7274 (0%) 1
    General disorders
    Adverse drug reaction 3/7266 (0%) 3 1/7274 (0%) 1
    Asthenia 2/7266 (0%) 2 3/7274 (0%) 3
    Chest pain 6/7266 (0.1%) 6 8/7274 (0.1%) 8
    Device dislocation 2/7266 (0%) 2 0/7274 (0%) 0
    Device malfunction 1/7266 (0%) 1 0/7274 (0%) 0
    Drug intolerance 1/7266 (0%) 1 0/7274 (0%) 0
    Fat necrosis 0/7266 (0%) 0 1/7274 (0%) 1
    Fatigue 0/7266 (0%) 0 1/7274 (0%) 1
    Gait disturbance 1/7266 (0%) 1 0/7274 (0%) 0
    Generalised oedema 1/7266 (0%) 1 0/7274 (0%) 0
    Granuloma 1/7266 (0%) 1 0/7274 (0%) 0
    Hernia 1/7266 (0%) 1 1/7274 (0%) 1
    Malaise 0/7266 (0%) 0 1/7274 (0%) 1
    Mucosal hyperaemia 0/7266 (0%) 0 1/7274 (0%) 1
    Multi-organ failure 2/7266 (0%) 2 0/7274 (0%) 0
    Non-cardiac chest pain 17/7266 (0.2%) 19 26/7274 (0.4%) 31
    Puncture site haemorrhage 1/7266 (0%) 1 0/7274 (0%) 0
    Pyrexia 1/7266 (0%) 1 0/7274 (0%) 0
    Spinal pain 1/7266 (0%) 1 0/7274 (0%) 0
    Submandibular mass 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatobiliary disorders
    Bile duct stone 1/7266 (0%) 1 0/7274 (0%) 0
    Biliary colic 1/7266 (0%) 1 1/7274 (0%) 1
    Biliary dyskinesia 1/7266 (0%) 1 0/7274 (0%) 0
    Cholecystitis 0/7266 (0%) 0 1/7274 (0%) 1
    Cholelithiasis 0/7266 (0%) 0 1/7274 (0%) 1
    Drug-induced liver injury 1/7266 (0%) 1 0/7274 (0%) 0
    Gallbladder polyp 0/7266 (0%) 0 1/7274 (0%) 1
    Hepatic cirrhosis 0/7266 (0%) 0 2/7274 (0%) 2
    Hepatic congestion 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatic cyst 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatic failure 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatic function abnormal 2/7266 (0%) 2 0/7274 (0%) 0
    Hepatitis 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatitis acute 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatitis toxic 0/7266 (0%) 0 1/7274 (0%) 1
    Immune system disorders
    Corneal graft rejection 1/7266 (0%) 2 0/7274 (0%) 0
    Drug hypersensitivity 0/7266 (0%) 0 1/7274 (0%) 1
    Infections and infestations
    Abdominal abscess 0/7266 (0%) 0 1/7274 (0%) 1
    Acute hepatitis B 1/7266 (0%) 1 0/7274 (0%) 0
    Appendicitis 0/7266 (0%) 0 2/7274 (0%) 2
    Appendicitis perforated 2/7266 (0%) 2 0/7274 (0%) 0
    Bronchitis 2/7266 (0%) 3 4/7274 (0.1%) 4
    Bursitis infective 0/7266 (0%) 0 1/7274 (0%) 1
    Dengue fever 2/7266 (0%) 2 0/7274 (0%) 0
    Diverticulitis 6/7266 (0.1%) 7 4/7274 (0.1%) 4
    Gastroenteritis 3/7266 (0%) 3 2/7274 (0%) 2
    Hepatitis C 3/7266 (0%) 3 0/7274 (0%) 0
    Hepatitis E 1/7266 (0%) 1 0/7274 (0%) 0
    Herpes simplex encephalitis 0/7266 (0%) 0 1/7274 (0%) 1
    Herpes zoster 1/7266 (0%) 1 1/7274 (0%) 1
    Infected bites 1/7266 (0%) 1 0/7274 (0%) 0
    Infective exacerbation of chronic obstructive airways disease 0/7266 (0%) 0 3/7274 (0%) 3
    Influenza 1/7266 (0%) 1 0/7274 (0%) 0
    Laryngitis 1/7266 (0%) 2 0/7274 (0%) 0
    Liver abscess 1/7266 (0%) 1 0/7274 (0%) 0
    Lower respiratory tract infection 1/7266 (0%) 1 0/7274 (0%) 0
    Lyme disease 0/7266 (0%) 0 1/7274 (0%) 1
    Mycetoma mycotic 1/7266 (0%) 1 0/7274 (0%) 0
    Oesophageal candidiasis 0/7266 (0%) 0 1/7274 (0%) 1
    Osteomyelitis 1/7266 (0%) 1 0/7274 (0%) 0
    Otitis media 0/7266 (0%) 0 1/7274 (0%) 1
    Otitis media chronic 2/7266 (0%) 2 0/7274 (0%) 0
    Pneumonia 0/7266 (0%) 0 1/7274 (0%) 1
    Postoperative wound infection 0/7266 (0%) 0 1/7274 (0%) 1
    Pulmonary tuberculosis 0/7266 (0%) 0 1/7274 (0%) 1
    Pyelonephritis 0/7266 (0%) 0 1/7274 (0%) 1
    Scrub typhus 1/7266 (0%) 1 0/7274 (0%) 0
    Sepsis 0/7266 (0%) 0 1/7274 (0%) 1
    Sialoadenitis 1/7266 (0%) 1 0/7274 (0%) 0
    Sinusitis 1/7266 (0%) 1 0/7274 (0%) 0
    Tooth abscess 1/7266 (0%) 1 0/7274 (0%) 0
    Typhoid fever 0/7266 (0%) 0 1/7274 (0%) 1
    Urosepsis 1/7266 (0%) 1 0/7274 (0%) 0
    Viral infection 1/7266 (0%) 1 0/7274 (0%) 0
    Wound infection 0/7266 (0%) 0 1/7274 (0%) 1
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence 1/7266 (0%) 1 0/7274 (0%) 0
    Accidental overdose 17/7266 (0.2%) 17 19/7274 (0.3%) 19
    Acetabulum fracture 2/7266 (0%) 2 0/7274 (0%) 0
    Alcohol poisoning 0/7266 (0%) 0 1/7274 (0%) 1
    Ankle fracture 6/7266 (0.1%) 6 3/7274 (0%) 3
    Arthropod bite 0/7266 (0%) 0 1/7274 (0%) 1
    Arthropod sting 1/7266 (0%) 1 0/7274 (0%) 0
    Avulsion fracture 0/7266 (0%) 0 1/7274 (0%) 1
    Brain contusion 3/7266 (0%) 3 0/7274 (0%) 0
    Burns second degree 1/7266 (0%) 1 0/7274 (0%) 0
    Burns third degree 1/7266 (0%) 1 0/7274 (0%) 0
    Cervical vertebral fracture 0/7266 (0%) 0 1/7274 (0%) 1
    Chemical burns of eye 1/7266 (0%) 1 0/7274 (0%) 0
    Comminuted fracture 0/7266 (0%) 0 1/7274 (0%) 1
    Concussion 0/7266 (0%) 0 4/7274 (0.1%) 4
    Contusion 1/7266 (0%) 1 2/7274 (0%) 2
    Craniocerebral injury 3/7266 (0%) 3 3/7274 (0%) 3
    Delayed recovery from anaesthesia 1/7266 (0%) 1 0/7274 (0%) 0
    Dislocation of vertebra 1/7266 (0%) 1 0/7274 (0%) 0
    Facial bones fracture 3/7266 (0%) 3 4/7274 (0.1%) 4
    Fall 9/7266 (0.1%) 9 9/7274 (0.1%) 9
    Femoral neck fracture 5/7266 (0.1%) 5 3/7274 (0%) 3
    Femur fracture 7/7266 (0.1%) 7 11/7274 (0.2%) 11
    Fibula fracture 3/7266 (0%) 3 1/7274 (0%) 1
    Foot fracture 4/7266 (0.1%) 4 1/7274 (0%) 1
    Forearm fracture 1/7266 (0%) 1 0/7274 (0%) 0
    Foreign body 0/7266 (0%) 0 2/7274 (0%) 2
    Fracture 1/7266 (0%) 1 0/7274 (0%) 0
    Fracture displacement 1/7266 (0%) 1 0/7274 (0%) 0
    Gastrointestinal stoma complication 0/7266 (0%) 0 1/7274 (0%) 1
    Hand fracture 0/7266 (0%) 0 1/7274 (0%) 1
    Head injury 5/7266 (0.1%) 5 2/7274 (0%) 2
    Heat stroke 0/7266 (0%) 0 1/7274 (0%) 1
    Hip fracture 5/7266 (0.1%) 5 6/7274 (0.1%) 6
    Humerus fracture 4/7266 (0.1%) 5 9/7274 (0.1%) 9
    Incisional hernia 2/7266 (0%) 2 1/7274 (0%) 1
    Intentional overdose 2/7266 (0%) 2 2/7274 (0%) 2
    Joint dislocation 0/7266 (0%) 0 2/7274 (0%) 2
    Laceration 4/7266 (0.1%) 4 2/7274 (0%) 2
    Ligament injury 1/7266 (0%) 1 0/7274 (0%) 0
    Ligament rupture 3/7266 (0%) 3 0/7274 (0%) 0
    Ligament sprain 1/7266 (0%) 1 2/7274 (0%) 2
    Limb traumatic amputation 1/7266 (0%) 1 0/7274 (0%) 0
    Lower limb fracture 4/7266 (0.1%) 4 2/7274 (0%) 2
    Lumbar vertebral fracture 3/7266 (0%) 3 2/7274 (0%) 2
    Meniscus injury 2/7266 (0%) 2 2/7274 (0%) 2
    Mouth injury 1/7266 (0%) 1 0/7274 (0%) 0
    Muscle injury 1/7266 (0%) 1 0/7274 (0%) 0
    Near drowning 1/7266 (0%) 1 0/7274 (0%) 0
    Overdose 2/7266 (0%) 2 2/7274 (0%) 2
    Patella fracture 2/7266 (0%) 2 1/7274 (0%) 1
    Pelvic fracture 2/7266 (0%) 2 0/7274 (0%) 0
    Periorbital haematoma 0/7266 (0%) 0 1/7274 (0%) 1
    Periprosthetic fracture 0/7266 (0%) 0 1/7274 (0%) 1
    Periprosthetic osteolysis 1/7266 (0%) 1 0/7274 (0%) 0
    Post procedural fistula 1/7266 (0%) 1 0/7274 (0%) 0
    Post procedural haemorrhage 2/7266 (0%) 2 3/7274 (0%) 3
    Postoperative ileus 0/7266 (0%) 0 1/7274 (0%) 1
    Postoperative wound complication 0/7266 (0%) 0 1/7274 (0%) 1
    Prescribed overdose 1/7266 (0%) 1 0/7274 (0%) 0
    Procedural complication 0/7266 (0%) 0 1/7274 (0%) 1
    Pubis fracture 0/7266 (0%) 0 2/7274 (0%) 2
    Pulmonary contusion 1/7266 (0%) 2 0/7274 (0%) 0
    Radius fracture 1/7266 (0%) 1 3/7274 (0%) 3
    Renal haematoma 1/7266 (0%) 1 0/7274 (0%) 0
    Rib fracture 2/7266 (0%) 2 5/7274 (0.1%) 5
    Road traffic accident 5/7266 (0.1%) 6 1/7274 (0%) 1
    Skull fracture 1/7266 (0%) 1 3/7274 (0%) 3
    Soft tissue injury 1/7266 (0%) 1 0/7274 (0%) 0
    Spinal column injury 0/7266 (0%) 0 1/7274 (0%) 1
    Spinal compression fracture 5/7266 (0.1%) 6 4/7274 (0.1%) 5
    Splinter 0/7266 (0%) 0 1/7274 (0%) 1
    Sternal fracture 1/7266 (0%) 1 0/7274 (0%) 0
    Subdural haematoma 2/7266 (0%) 2 4/7274 (0.1%) 4
    Subdural haemorrhage 1/7266 (0%) 1 0/7274 (0%) 0
    Tendon rupture 1/7266 (0%) 1 5/7274 (0.1%) 5
    Testicular injury 0/7266 (0%) 0 1/7274 (0%) 1
    Thermal burn 0/7266 (0%) 0 1/7274 (0%) 1
    Thoracic vertebral fracture 1/7266 (0%) 1 0/7274 (0%) 0
    Tibia fracture 1/7266 (0%) 1 1/7274 (0%) 1
    Tongue injury 1/7266 (0%) 1 0/7274 (0%) 0
    Toxicity to various agents 5/7266 (0.1%) 5 0/7274 (0%) 0
    Tracheal injury 0/7266 (0%) 0 1/7274 (0%) 1
    Traumatic intracranial haemorrhage 1/7266 (0%) 1 1/7274 (0%) 1
    Ulnar nerve injury 1/7266 (0%) 1 0/7274 (0%) 0
    Upper limb fracture 1/7266 (0%) 1 3/7274 (0%) 3
    Urinary bladder rupture 0/7266 (0%) 0 1/7274 (0%) 1
    Vascular pseudoaneurysm 0/7266 (0%) 0 1/7274 (0%) 1
    Wrist fracture 4/7266 (0.1%) 4 0/7274 (0%) 0
    Investigations
    Anticoagulation drug level increased 1/7266 (0%) 1 0/7274 (0%) 0
    Haemoglobin decreased 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatic enzyme abnormal 0/7266 (0%) 0 1/7274 (0%) 1
    Hepatic enzyme increased 0/7266 (0%) 0 2/7274 (0%) 2
    International normalised ratio increased 1/7266 (0%) 1 0/7274 (0%) 0
    Prostatic specific antigen increased 0/7266 (0%) 0 1/7274 (0%) 1
    White blood cell count increased 0/7266 (0%) 0 1/7274 (0%) 1
    Metabolism and nutrition disorders
    Decreased appetite 1/7266 (0%) 1 0/7274 (0%) 0
    Dehydration 5/7266 (0.1%) 5 8/7274 (0.1%) 8
    Electrolyte imbalance 0/7266 (0%) 0 1/7274 (0%) 1
    Failure to thrive 2/7266 (0%) 2 2/7274 (0%) 2
    Hyperkalaemia 8/7266 (0.1%) 9 5/7274 (0.1%) 5
    Hypoalbuminaemia 0/7266 (0%) 0 1/7274 (0%) 1
    Hypochloraemia 2/7266 (0%) 2 1/7274 (0%) 1
    Hypokalaemia 3/7266 (0%) 3 4/7274 (0.1%) 4
    Hyponatraemia 8/7266 (0.1%) 9 21/7274 (0.3%) 21
    Hypophagia 1/7266 (0%) 1 0/7274 (0%) 0
    Hypophosphataemia 0/7266 (0%) 0 1/7274 (0%) 1
    Hypovolaemia 0/7266 (0%) 0 1/7274 (0%) 1
    Obesity 1/7266 (0%) 1 1/7274 (0%) 1
    Musculoskeletal and connective tissue disorders
    Ankle impingement 2/7266 (0%) 2 0/7274 (0%) 0
    Arthralgia 2/7266 (0%) 2 1/7274 (0%) 1
    Arthritis 0/7266 (0%) 0 1/7274 (0%) 2
    Arthritis reactive 2/7266 (0%) 2 0/7274 (0%) 0
    Arthropathy 1/7266 (0%) 1 1/7274 (0%) 1
    Back pain 6/7266 (0.1%) 6 4/7274 (0.1%) 5
    Bursitis 1/7266 (0%) 1 1/7274 (0%) 1
    Chondrocalcinosis 0/7266 (0%) 0 1/7274 (0%) 1
    Compartment syndrome 1/7266 (0%) 1 1/7274 (0%) 1
    Dupuytren's contracture 1/7266 (0%) 1 3/7274 (0%) 4
    Gouty arthritis 1/7266 (0%) 1 0/7274 (0%) 0
    Haemarthrosis 1/7266 (0%) 1 0/7274 (0%) 0
    Intervertebral disc compression 1/7266 (0%) 1 0/7274 (0%) 0
    Intervertebral disc disorder 1/7266 (0%) 1 1/7274 (0%) 1
    Intervertebral disc displacement 1/7266 (0%) 1 2/7274 (0%) 2
    Intervertebral disc protrusion 8/7266 (0.1%) 9 8/7274 (0.1%) 8
    Joint effusion 1/7266 (0%) 1 1/7274 (0%) 1
    Joint swelling 0/7266 (0%) 0 1/7274 (0%) 1
    Lumbar spinal stenosis 13/7266 (0.2%) 14 5/7274 (0.1%) 5
    Musculoskeletal chest pain 5/7266 (0.1%) 5 6/7274 (0.1%) 6
    Musculoskeletal pain 1/7266 (0%) 1 3/7274 (0%) 3
    Myalgia 1/7266 (0%) 1 0/7274 (0%) 0
    Osteitis 1/7266 (0%) 1 0/7274 (0%) 0
    Osteoarthritis 52/7266 (0.7%) 54 35/7274 (0.5%) 37
    Osteochondrosis 2/7266 (0%) 2 2/7274 (0%) 2
    Osteoporosis 2/7266 (0%) 2 0/7274 (0%) 0
    Pain in extremity 1/7266 (0%) 1 0/7274 (0%) 0
    Polymyalgia rheumatica 1/7266 (0%) 1 0/7274 (0%) 0
    Psoriatic arthropathy 1/7266 (0%) 1 0/7274 (0%) 0
    Rheumatoid arthritis 1/7266 (0%) 1 1/7274 (0%) 1
    Rotator cuff syndrome 6/7266 (0.1%) 6 7/7274 (0.1%) 7
    Spinal column stenosis 4/7266 (0.1%) 4 3/7274 (0%) 3
    Spinal osteoarthritis 7/7266 (0.1%) 7 5/7274 (0.1%) 5
    Spondylolisthesis 2/7266 (0%) 2 1/7274 (0%) 1
    Synovial cyst 0/7266 (0%) 0 1/7274 (0%) 1
    Tenosynovitis 0/7266 (0%) 0 1/7274 (0%) 1
    Tenosynovitis stenosans 0/7266 (0%) 0 1/7274 (0%) 1
    Trigger finger 2/7266 (0%) 2 0/7274 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm 0/7266 (0%) 0 1/7274 (0%) 1
    Acute myeloid leukaemia 1/7266 (0%) 1 1/7274 (0%) 1
    Adenocarcinoma 1/7266 (0%) 1 1/7274 (0%) 1
    Adenocarcinoma gastric 2/7266 (0%) 2 2/7274 (0%) 2
    Adenocarcinoma of appendix 1/7266 (0%) 1 0/7274 (0%) 0
    Adenocarcinoma of colon 11/7266 (0.2%) 11 12/7274 (0.2%) 12
    Adenocarcinoma of salivary gland 0/7266 (0%) 0 1/7274 (0%) 1
    Adenocarcinoma of the cervix 1/7266 (0%) 1 0/7274 (0%) 0
    Adenocarcinoma pancreas 2/7266 (0%) 2 2/7274 (0%) 2
    Adenoid cystic carcinoma 1/7266 (0%) 1 0/7274 (0%) 0
    Adenolymphoma 1/7266 (0%) 1 0/7274 (0%) 0
    Anal cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Anal squamous cell carcinoma 0/7266 (0%) 0 1/7274 (0%) 1
    Anaplastic large-cell lymphoma 0/7266 (0%) 0 1/7274 (0%) 1
    Angioimmunoblastic T-cell lymphoma 0/7266 (0%) 0 1/7274 (0%) 1
    B-cell lymphoma 0/7266 (0%) 0 4/7274 (0.1%) 5
    Basal cell carcinoma 44/7266 (0.6%) 50 55/7274 (0.8%) 86
    Basosquamous carcinoma 1/7266 (0%) 1 0/7274 (0%) 0
    Benign gastric neoplasm 1/7266 (0%) 1 0/7274 (0%) 0
    Benign salivary gland neoplasm 1/7266 (0%) 1 0/7274 (0%) 0
    Bile duct cancer 3/7266 (0%) 3 0/7274 (0%) 0
    Bladder cancer 15/7266 (0.2%) 15 10/7274 (0.1%) 10
    Bladder cancer recurrent 1/7266 (0%) 1 0/7274 (0%) 0
    Bladder neoplasm 2/7266 (0%) 2 2/7274 (0%) 2
    Bladder papilloma 1/7266 (0%) 1 0/7274 (0%) 0
    Bladder transitional cell carcinoma 6/7266 (0.1%) 6 6/7274 (0.1%) 6
    Bone cancer 1/7266 (0%) 1 0/7274 (0%) 0
    Bone neoplasm 1/7266 (0%) 1 0/7274 (0%) 0
    Bone sarcoma 0/7266 (0%) 0 1/7274 (0%) 1
    Bowen's disease 4/7266 (0.1%) 4 2/7274 (0%) 2
    Breast cancer 5/7266 (0.1%) 5 5/7274 (0.1%) 5
    Breast cancer in situ 1/7266 (0%) 1 1/7274 (0%) 1
    Breast cancer metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Breast cancer recurrent 0/7266 (0%) 0 1/7274 (0%) 1
    Bronchial carcinoma 3/7266 (0%) 3 1/7274 (0%) 1
    Carcinoid tumour of the small bowel 0/7266 (0%) 0 1/7274 (0%) 1
    Carcinoid tumour pulmonary 0/7266 (0%) 0 1/7274 (0%) 1
    Central nervous system lymphoma 1/7266 (0%) 1 0/7274 (0%) 0
    Cervix carcinoma 2/7266 (0%) 2 0/7274 (0%) 0
    Cholangiocarcinoma 1/7266 (0%) 1 4/7274 (0.1%) 4
    Cholesteatoma 1/7266 (0%) 1 0/7274 (0%) 0
    Chronic lymphocytic leukaemia 4/7266 (0.1%) 4 3/7274 (0%) 3
    Chronic lymphocytic leukaemia recurrent 0/7266 (0%) 0 1/7274 (0%) 1
    Chronic myeloid leukaemia 0/7266 (0%) 0 3/7274 (0%) 3
    Clear cell renal cell carcinoma 0/7266 (0%) 0 1/7274 (0%) 1
    Colon adenoma 4/7266 (0.1%) 4 1/7274 (0%) 1
    Colon cancer 11/7266 (0.2%) 11 14/7274 (0.2%) 14
    Colon cancer metastatic 1/7266 (0%) 1 2/7274 (0%) 2
    Colon cancer stage I 1/7266 (0%) 1 0/7274 (0%) 0
    Colon cancer stage IV 1/7266 (0%) 1 2/7274 (0%) 2
    Colon neoplasm 1/7266 (0%) 1 1/7274 (0%) 1
    Colorectal adenocarcinoma 1/7266 (0%) 1 2/7274 (0%) 2
    Colorectal cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Diffuse large B-cell lymphoma 2/7266 (0%) 2 0/7274 (0%) 0
    Endometrial adenocarcinoma 1/7266 (0%) 1 5/7274 (0.1%) 5
    Endometrial cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Gallbladder cancer 1/7266 (0%) 1 0/7274 (0%) 0
    Gastric adenoma 1/7266 (0%) 1 0/7274 (0%) 0
    Gastric cancer 5/7266 (0.1%) 5 2/7274 (0%) 2
    Gastric cancer recurrent 1/7266 (0%) 1 1/7274 (0%) 1
    Gastric cancer stage IV 1/7266 (0%) 1 0/7274 (0%) 0
    Gastrointestinal cancer metastatic 1/7266 (0%) 1 0/7274 (0%) 0
    Gastrointestinal carcinoma 0/7266 (0%) 0 1/7274 (0%) 1
    Gastrointestinal tract adenoma 1/7266 (0%) 1 0/7274 (0%) 0
    Glioblastoma multiforme 1/7266 (0%) 1 1/7274 (0%) 1
    Glioma 1/7266 (0%) 1 0/7274 (0%) 0
    Hepatic cancer 1/7266 (0%) 1 2/7274 (0%) 2
    Hepatic cancer metastatic 2/7266 (0%) 2 0/7274 (0%) 0
    Hepatic neoplasm 0/7266 (0%) 0 1/7274 (0%) 1
    Hepatocellular carcinoma 1/7266 (0%) 1 3/7274 (0%) 3
    Intraductal papilloma of breast 0/7266 (0%) 0 1/7274 (0%) 1
    Intraductal proliferative breast lesion 1/7266 (0%) 1 2/7274 (0%) 2
    Intraocular melanoma 1/7266 (0%) 1 0/7274 (0%) 0
    Invasive ductal breast carcinoma 2/7266 (0%) 2 4/7274 (0.1%) 4
    Laryngeal cancer 0/7266 (0%) 0 4/7274 (0.1%) 4
    Laryngeal squamous cell carcinoma 2/7266 (0%) 3 0/7274 (0%) 0
    Leiomyosarcoma 0/7266 (0%) 0 1/7274 (0%) 1
    Leiomyosarcoma metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Lentigo maligna 1/7266 (0%) 1 1/7274 (0%) 1
    Leukaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Lip and/or oral cavity cancer 2/7266 (0%) 2 0/7274 (0%) 0
    Lip squamous cell carcinoma 1/7266 (0%) 1 0/7274 (0%) 0
    Lipoma 1/7266 (0%) 1 0/7274 (0%) 0
    Lung adenocarcinoma 6/7266 (0.1%) 6 4/7274 (0.1%) 4
    Lung adenocarcinoma metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Lung adenocarcinoma stage I 0/7266 (0%) 0 1/7274 (0%) 1
    Lung adenocarcinoma stage IV 1/7266 (0%) 1 0/7274 (0%) 0
    Lung cancer metastatic 2/7266 (0%) 2 4/7274 (0.1%) 4
    Lung carcinoma cell type unspecified stage IV 3/7266 (0%) 3 0/7274 (0%) 0
    Lung neoplasm 1/7266 (0%) 1 1/7274 (0%) 1
    Lung neoplasm malignant 12/7266 (0.2%) 12 12/7274 (0.2%) 12
    Lung squamous cell carcinoma stage III 1/7266 (0%) 1 0/7274 (0%) 0
    Lymphocytic leukaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Malignant melanoma 10/7266 (0.1%) 10 6/7274 (0.1%) 7
    Malignant melanoma in situ 2/7266 (0%) 2 4/7274 (0.1%) 4
    Malignant neoplasm of ampulla of Vater 2/7266 (0%) 2 0/7274 (0%) 0
    Malignant neoplasm of renal pelvis 0/7266 (0%) 0 1/7274 (0%) 1
    Melanocytic naevus 0/7266 (0%) 0 1/7274 (0%) 1
    Meningeal neoplasm 0/7266 (0%) 0 1/7274 (0%) 1
    Meningioma 1/7266 (0%) 1 0/7274 (0%) 0
    Meningioma malignant 0/7266 (0%) 0 1/7274 (0%) 1
    Metastases to bone 2/7266 (0%) 2 0/7274 (0%) 0
    Metastases to central nervous system 1/7266 (0%) 1 1/7274 (0%) 1
    Metastases to liver 1/7266 (0%) 1 0/7274 (0%) 0
    Metastases to spine 1/7266 (0%) 1 0/7274 (0%) 0
    Metastatic bronchial carcinoma 1/7266 (0%) 1 0/7274 (0%) 0
    Metastatic malignant melanoma 0/7266 (0%) 0 1/7274 (0%) 1
    Metastatic renal cell carcinoma 1/7266 (0%) 1 0/7274 (0%) 0
    Metastatic squamous cell carcinoma 1/7266 (0%) 1 0/7274 (0%) 0
    Metastatic uterine cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Mucinous adenocarcinoma of appendix 0/7266 (0%) 0 1/7274 (0%) 1
    Myelodysplastic syndrome 3/7266 (0%) 3 1/7274 (0%) 1
    Nasal cavity cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Nasopharyngeal cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Neoplasm recurrence 0/7266 (0%) 0 1/7274 (0%) 1
    Neuroendocrine carcinoma metastatic 1/7266 (0%) 1 0/7274 (0%) 0
    Neuroendocrine tumour 1/7266 (0%) 1 1/7274 (0%) 1
    Neurofibroma 0/7266 (0%) 0 1/7274 (0%) 1
    Non-Hodgkin's lymphoma 6/7266 (0.1%) 6 1/7274 (0%) 1
    Non-small cell lung cancer 2/7266 (0%) 2 2/7274 (0%) 2
    Non-small cell lung cancer metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Oesophageal adenocarcinoma 2/7266 (0%) 2 1/7274 (0%) 1
    Oesophageal carcinoma 1/7266 (0%) 1 3/7274 (0%) 3
    Oesophageal squamous cell carcinoma 0/7266 (0%) 0 2/7274 (0%) 2
    Oropharyngeal squamous cell carcinoma 0/7266 (0%) 0 1/7274 (0%) 1
    Ovarian adenoma 1/7266 (0%) 1 1/7274 (0%) 1
    Ovarian cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Ovarian cancer metastatic 1/7266 (0%) 1 1/7274 (0%) 1
    Ovarian germ cell teratoma benign 0/7266 (0%) 0 1/7274 (0%) 1
    Ovarian granulosa-theca cell tumour 1/7266 (0%) 1 0/7274 (0%) 0
    Ovarian neoplasm 0/7266 (0%) 0 1/7274 (0%) 1
    Pancreatic carcinoma 8/7266 (0.1%) 8 7/7274 (0.1%) 7
    Pancreatic carcinoma metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Papillary thyroid cancer 1/7266 (0%) 1 1/7274 (0%) 1
    Parathyroid tumour benign 0/7266 (0%) 0 1/7274 (0%) 1
    Penile cancer 0/7266 (0%) 0 2/7274 (0%) 2
    Penile squamous cell carcinoma 1/7266 (0%) 1 1/7274 (0%) 1
    Phaeochromocytoma 0/7266 (0%) 0 1/7274 (0%) 1
    Pituitary tumour 0/7266 (0%) 0 1/7274 (0%) 1
    Pituitary tumour benign 0/7266 (0%) 0 1/7274 (0%) 1
    Plasma cell myeloma 1/7266 (0%) 1 6/7274 (0.1%) 6
    Plasmablastic lymphoma 1/7266 (0%) 1 0/7274 (0%) 0
    Plasmacytoma 1/7266 (0%) 1 0/7274 (0%) 0
    Pleomorphic liposarcoma 0/7266 (0%) 0 1/7274 (0%) 1
    Pleural mesothelioma 1/7266 (0%) 1 0/7274 (0%) 0
    Polycythaemia vera 0/7266 (0%) 0 1/7274 (0%) 1
    Prostate cancer 36/7266 (0.5%) 36 45/7274 (0.6%) 45
    Prostate cancer metastatic 5/7266 (0.1%) 5 5/7274 (0.1%) 5
    Prostate cancer recurrent 3/7266 (0%) 3 2/7274 (0%) 2
    Prostate cancer stage I 1/7266 (0%) 1 0/7274 (0%) 0
    Prostatic adenoma 1/7266 (0%) 1 2/7274 (0%) 2
    Rectal adenocarcinoma 1/7266 (0%) 1 2/7274 (0%) 2
    Rectal cancer 2/7266 (0%) 2 4/7274 (0.1%) 4
    Rectal cancer metastatic 1/7266 (0%) 1 0/7274 (0%) 0
    Rectosigmoid cancer 1/7266 (0%) 1 0/7274 (0%) 0
    Renal cancer 7/7266 (0.1%) 7 3/7274 (0%) 3
    Renal cancer metastatic 2/7266 (0%) 2 0/7274 (0%) 0
    Renal cell carcinoma 3/7266 (0%) 3 2/7274 (0%) 2
    Renal cell carcinoma recurrent 1/7266 (0%) 1 0/7274 (0%) 0
    Renal cell carcinoma stage I 1/7266 (0%) 1 0/7274 (0%) 0
    Renal cell carcinoma stage III 1/7266 (0%) 1 0/7274 (0%) 0
    Renal neoplasm 1/7266 (0%) 1 1/7274 (0%) 1
    Renal oncocytoma 1/7266 (0%) 1 0/7274 (0%) 0
    Retroperitoneal cancer 1/7266 (0%) 1 0/7274 (0%) 0
    Sarcoma 1/7266 (0%) 1 1/7274 (0%) 1
    Skin cancer 1/7266 (0%) 1 3/7274 (0%) 5
    Small cell lung cancer 1/7266 (0%) 1 1/7274 (0%) 1
    Squamous cell carcinoma 26/7266 (0.4%) 38 38/7274 (0.5%) 44
    Squamous cell carcinoma of head and neck 0/7266 (0%) 0 1/7274 (0%) 1
    Squamous cell carcinoma of lung 2/7266 (0%) 2 7/7274 (0.1%) 7
    Squamous cell carcinoma of skin 12/7266 (0.2%) 13 20/7274 (0.3%) 23
    Squamous cell carcinoma of the oral cavity 0/7266 (0%) 0 1/7274 (0%) 1
    Squamous cell carcinoma of the tongue 2/7266 (0%) 2 1/7274 (0%) 1
    T-cell lymphoma 0/7266 (0%) 0 1/7274 (0%) 1
    T-cell prolymphocytic leukaemia 1/7266 (0%) 1 0/7274 (0%) 0
    Testis cancer 0/7266 (0%) 0 1/7274 (0%) 1
    Thymic cancer metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Thyroid adenoma 0/7266 (0%) 0 1/7274 (0%) 1
    Thyroid cancer 2/7266 (0%) 2 0/7274 (0%) 0
    Tongue cancer recurrent 0/7266 (0%) 0 1/7274 (0%) 1
    Tongue neoplasm malignant stage unspecified 0/7266 (0%) 0 1/7274 (0%) 1
    Tonsil cancer 1/7266 (0%) 1 0/7274 (0%) 0
    Tonsil cancer metastatic 0/7266 (0%) 0 1/7274 (0%) 1
    Tracheal cancer 1/7266 (0%) 1 0/7274 (0%) 0
    Tracheal neoplasm 1/7266 (0%) 1 0/7274 (0%) 0
    Transitional cell carcinoma 7/7266 (0.1%) 8 7/7274 (0.1%) 7
    Urethral neoplasm 1/7266 (0%) 1 0/7274 (0%) 0
    Uterine cancer 1/7266 (0%) 1 4/7274 (0.1%) 4
    Uterine leiomyoma 0/7266 (0%) 0 1/7274 (0%) 1
    Nervous system disorders
    Acoustic neuritis 0/7266 (0%) 0 1/7274 (0%) 1
    Arachnoid cyst 1/7266 (0%) 1 1/7274 (0%) 1
    Ataxia 0/7266 (0%) 0 2/7274 (0%) 2
    Basal ganglia haemorrhage 1/7266 (0%) 1 0/7274 (0%) 0
    Brain injury 1/7266 (0%) 1 0/7274 (0%) 0
    Carpal tunnel syndrome 1/7266 (0%) 1 2/7274 (0%) 2
    Cauda equina syndrome 0/7266 (0%) 0 2/7274 (0%) 2
    Central nervous system lesion 1/7266 (0%) 1 1/7274 (0%) 1
    Cervical cord compression 0/7266 (0%) 0 1/7274 (0%) 1
    Cervical myelopathy 0/7266 (0%) 0 3/7274 (0%) 3
    Cervical radiculopathy 1/7266 (0%) 1 1/7274 (0%) 1
    Cervicobrachial syndrome 1/7266 (0%) 1 0/7274 (0%) 0
    Cognitive disorder 2/7266 (0%) 2 0/7274 (0%) 0
    Complex partial seizures 1/7266 (0%) 1 0/7274 (0%) 0
    Convulsion 5/7266 (0.1%) 5 6/7274 (0.1%) 6
    Cubital tunnel syndrome 1/7266 (0%) 1 0/7274 (0%) 0
    Dementia 0/7266 (0%) 0 2/7274 (0%) 2
    Dementia Alzheimer's type 2/7266 (0%) 2 1/7274 (0%) 1
    Dizziness 7/7266 (0.1%) 7 1/7274 (0%) 1
    Dizziness postural 0/7266 (0%) 0 1/7274 (0%) 1
    Encephalopathy 0/7266 (0%) 0 2/7274 (0%) 3
    Epilepsy 2/7266 (0%) 3 3/7274 (0%) 3
    Facial paresis 1/7266 (0%) 1 0/7274 (0%) 0
    Haemorrhage intracranial 0/7266 (0%) 0 1/7274 (0%) 1
    Headache 1/7266 (0%) 1 1/7274 (0%) 1
    Hypersomnia 1/7266 (0%) 1 0/7274 (0%) 0
    Intracranial aneurysm 0/7266 (0%) 0 1/7274 (0%) 1
    Loss of consciousness 0/7266 (0%) 0 1/7274 (0%) 1
    Lumbar radiculopathy 3/7266 (0%) 3 1/7274 (0%) 1
    Migraine 1/7266 (0%) 1 1/7274 (0%) 1
    Monoplegia 0/7266 (0%) 0 1/7274 (0%) 1
    Myasthenia gravis 1/7266 (0%) 1 0/7274 (0%) 0
    Myasthenia gravis crisis 1/7266 (0%) 1 0/7274 (0%) 0
    Myelopathy 0/7266 (0%) 0 2/7274 (0%) 2
    Nerve compression 0/7266 (0%) 0 1/7274 (0%) 1
    Nerve root compression 1/7266 (0%) 1 0/7274 (0%) 0
    Nervous system disorder 1/7266 (0%) 1 0/7274 (0%) 0
    Neuralgia 1/7266 (0%) 1 0/7274 (0%) 0
    Neurological symptom 0/7266 (0%) 0 1/7274 (0%) 1
    Neuropathy peripheral 0/7266 (0%) 0 1/7274 (0%) 1
    Normal pressure hydrocephalus 0/7266 (0%) 0 1/7274 (0%) 1
    Parkinson's disease 2/7266 (0%) 2 3/7274 (0%) 3
    Partial seizures 1/7266 (0%) 1 3/7274 (0%) 3
    Peripheral sensorimotor neuropathy 0/7266 (0%) 0 1/7274 (0%) 1
    Petit mal epilepsy 0/7266 (0%) 0 1/7274 (0%) 1
    Piriformis syndrome 0/7266 (0%) 0 1/7274 (0%) 1
    Posterior reversible encephalopathy syndrome 0/7266 (0%) 0 1/7274 (0%) 1
    Postictal state 1/7266 (0%) 1 0/7274 (0%) 0
    Radiculitis lumbosacral 1/7266 (0%) 1 0/7274 (0%) 0
    Retrograde amnesia 1/7266 (0%) 1 0/7274 (0%) 0
    Sciatica 2/7266 (0%) 2 4/7274 (0.1%) 4
    Sensory disturbance 0/7266 (0%) 0 1/7274 (0%) 1
    Spinal cord disorder 0/7266 (0%) 0 1/7274 (0%) 1
    Subarachnoid haemorrhage 1/7266 (0%) 1 1/7274 (0%) 1
    Subdural effusion 0/7266 (0%) 0 1/7274 (0%) 1
    Syncope 1/7266 (0%) 1 1/7274 (0%) 1
    Thoracic outlet syndrome 0/7266 (0%) 0 1/7274 (0%) 1
    Ulnar tunnel syndrome 0/7266 (0%) 0 1/7274 (0%) 1
    Vascular dementia 0/7266 (0%) 0 1/7274 (0%) 1
    Vertebrobasilar insufficiency 0/7266 (0%) 0 1/7274 (0%) 1
    Vertigo CNS origin 0/7266 (0%) 0 1/7274 (0%) 1
    Psychiatric disorders
    Alcohol abuse 0/7266 (0%) 0 1/7274 (0%) 1
    Anxiety 0/7266 (0%) 0 3/7274 (0%) 3
    Delirium 1/7266 (0%) 1 0/7274 (0%) 0
    Depression 4/7266 (0.1%) 4 3/7274 (0%) 3
    Dissociative disorder 0/7266 (0%) 0 1/7274 (0%) 1
    Drug abuse 1/7266 (0%) 1 0/7274 (0%) 0
    Drug dependence 1/7266 (0%) 1 0/7274 (0%) 0
    Major depression 2/7266 (0%) 2 3/7274 (0%) 4
    Mental status changes 1/7266 (0%) 1 0/7274 (0%) 0
    Nicotine dependence 1/7266 (0%) 1 0/7274 (0%) 0
    Paranoid personality disorder 1/7266 (0%) 1 0/7274 (0%) 0
    Suicidal ideation 2/7266 (0%) 2 0/7274 (0%) 0
    Suicide attempt 1/7266 (0%) 1 2/7274 (0%) 2
    Renal and urinary disorders
    Bladder outlet obstruction 0/7266 (0%) 0 1/7274 (0%) 1
    Bladder stenosis 0/7266 (0%) 0 1/7274 (0%) 1
    Calculus bladder 1/7266 (0%) 2 1/7274 (0%) 1
    Calculus ureteric 6/7266 (0.1%) 8 6/7274 (0.1%) 6
    Calculus urinary 2/7266 (0%) 2 4/7274 (0.1%) 4
    Haematuria 6/7266 (0.1%) 6 6/7274 (0.1%) 6
    Hydronephrosis 3/7266 (0%) 3 0/7274 (0%) 0
    Nephrolithiasis 10/7266 (0.1%) 10 9/7274 (0.1%) 11
    Renal artery stenosis 1/7266 (0%) 1 0/7274 (0%) 0
    Renal colic 4/7266 (0.1%) 4 4/7274 (0.1%) 5
    Renal cyst 0/7266 (0%) 0 1/7274 (0%) 1
    Renal failure 0/7266 (0%) 0 1/7274 (0%) 1
    Renal failure acute 2/7266 (0%) 2 1/7274 (0%) 1
    Renal impairment 0/7266 (0%) 0 1/7274 (0%) 1
    Renal tubular necrosis 1/7266 (0%) 1 0/7274 (0%) 0
    Stag horn calculus 0/7266 (0%) 0 1/7274 (0%) 1
    Tubulointerstitial nephritis 1/7266 (0%) 1 0/7274 (0%) 0
    Ureteric obstruction 0/7266 (0%) 0 1/7274 (0%) 1
    Urethral stenosis 1/7266 (0%) 1 4/7274 (0.1%) 4
    Urinary bladder polyp 1/7266 (0%) 1 0/7274 (0%) 0
    Urinary incontinence 0/7266 (0%) 0 1/7274 (0%) 1
    Urinary retention 4/7266 (0.1%) 4 6/7274 (0.1%) 7
    Reproductive system and breast disorders
    Atrophic vulvovaginitis 1/7266 (0%) 1 0/7274 (0%) 0
    Benign prostatic hyperplasia 15/7266 (0.2%) 15 11/7274 (0.2%) 11
    Calculus prostatic 1/7266 (0%) 1 0/7274 (0%) 0
    Cervical polyp 0/7266 (0%) 0 1/7274 (0%) 1
    Epididymal cyst 1/7266 (0%) 1 0/7274 (0%) 0
    Epididymitis 0/7266 (0%) 0 1/7274 (0%) 1
    Genital rash 1/7266 (0%) 1 0/7274 (0%) 0
    Metrorrhagia 1/7266 (0%) 1 0/7274 (0%) 0
    Orchitis noninfective 0/7266 (0%) 0 1/7274 (0%) 1
    Ovarian cyst 0/7266 (0%) 0 1/7274 (0%) 1
    Pelvic floor muscle weakness 1/7266 (0%) 1 0/7274 (0%) 0
    Postmenopausal haemorrhage 2/7266 (0%) 2 2/7274 (0%) 2
    Prostatic obstruction 0/7266 (0%) 0 1/7274 (0%) 1
    Prostatism 1/7266 (0%) 1 0/7274 (0%) 0
    Prostatitis 1/7266 (0%) 1 0/7274 (0%) 0
    Prostatomegaly 4/7266 (0.1%) 4 3/7274 (0%) 3
    Uterine polyp 1/7266 (0%) 1 0/7274 (0%) 0
    Uterovaginal prolapse 1/7266 (0%) 1 0/7274 (0%) 0
    Vaginal haemorrhage 1/7266 (0%) 1 0/7274 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 1/7266 (0%) 1 3/7274 (0%) 4
    Acute respiratory distress syndrome 1/7266 (0%) 1 1/7274 (0%) 1
    Acute respiratory failure 1/7266 (0%) 1 5/7274 (0.1%) 5
    Alveolitis 0/7266 (0%) 0 1/7274 (0%) 1
    Alveolitis allergic 0/7266 (0%) 0 1/7274 (0%) 1
    Asthma 8/7266 (0.1%) 10 4/7274 (0.1%) 4
    Atelectasis 1/7266 (0%) 1 0/7274 (0%) 0
    Bronchiectasis 1/7266 (0%) 1 1/7274 (0%) 1
    Chronic obstructive pulmonary disease 13/7266 (0.2%) 18 30/7274 (0.4%) 37
    Chronic respiratory disease 1/7266 (0%) 1 0/7274 (0%) 0
    Cough 0/7266 (0%) 0 1/7274 (0%) 1
    Dyspnoea 2/7266 (0%) 2 1/7274 (0%) 1
    Emphysema 1/7266 (0%) 1 3/7274 (0%) 3
    Epistaxis 9/7266 (0.1%) 9 6/7274 (0.1%) 9
    Haemoptysis 1/7266 (0%) 1 2/7274 (0%) 3
    Haemothorax 1/7266 (0%) 1 1/7274 (0%) 1
    Hydrothorax 0/7266 (0%) 0 1/7274 (0%) 1
    Hyperventilation 1/7266 (0%) 1 0/7274 (0%) 0
    Hypoxia 1/7266 (0%) 1 2/7274 (0%) 2
    Idiopathic pulmonary fibrosis 1/7266 (0%) 1 0/7274 (0%) 0
    Interstitial lung disease 2/7266 (0%) 2 1/7274 (0%) 1
    Laryngeal cyst 1/7266 (0%) 1 0/7274 (0%) 0
    Lung disorder 1/7266 (0%) 1 0/7274 (0%) 0
    Nasal obstruction 0/7266 (0%) 0 1/7274 (0%) 1
    Nasal polyps 0/7266 (0%) 0 2/7274 (0%) 2
    Orthopnoea 1/7266 (0%) 1 0/7274 (0%) 0
    Pleural effusion 4/7266 (0.1%) 4 2/7274 (0%) 2
    Pleuritic pain 1/7266 (0%) 2 0/7274 (0%) 0
    Pneumothorax 3/7266 (0%) 3 4/7274 (0.1%) 4
    Productive cough 0/7266 (0%) 0 1/7274 (0%) 1
    Pulmonary alveolar haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Pulmonary arterial hypertension 1/7266 (0%) 1 0/7274 (0%) 0
    Pulmonary embolism 1/7266 (0%) 1 0/7274 (0%) 0
    Pulmonary fibrosis 2/7266 (0%) 2 2/7274 (0%) 2
    Pulmonary hypertension 1/7266 (0%) 1 1/7274 (0%) 1
    Pulmonary oedema 3/7266 (0%) 3 2/7274 (0%) 3
    Respiratory distress 1/7266 (0%) 1 0/7274 (0%) 0
    Respiratory failure 4/7266 (0.1%) 4 0/7274 (0%) 0
    Sinus polyp 0/7266 (0%) 0 1/7274 (0%) 1
    Sleep apnoea syndrome 2/7266 (0%) 2 0/7274 (0%) 0
    Stridor 1/7266 (0%) 1 0/7274 (0%) 0
    Tracheal disorder 0/7266 (0%) 0 1/7274 (0%) 1
    Skin and subcutaneous tissue disorders
    Angioedema 1/7266 (0%) 2 0/7274 (0%) 0
    Decubitus ulcer 0/7266 (0%) 0 1/7274 (0%) 1
    Dermatitis contact 0/7266 (0%) 0 1/7274 (0%) 1
    Dermatitis psoriasiform 1/7266 (0%) 1 0/7274 (0%) 0
    Eczema asteatotic 1/7266 (0%) 1 0/7274 (0%) 0
    Hyperkeratosis 1/7266 (0%) 1 0/7274 (0%) 0
    Lichen sclerosus 1/7266 (0%) 1 0/7274 (0%) 0
    Pemphigoid 1/7266 (0%) 4 0/7274 (0%) 0
    Pruritus 1/7266 (0%) 1 0/7274 (0%) 0
    Rash 1/7266 (0%) 1 0/7274 (0%) 0
    Vascular disorders
    Angiodysplasia 1/7266 (0%) 1 0/7274 (0%) 0
    Aortic dissection 0/7266 (0%) 0 1/7274 (0%) 1
    Aortic stenosis 1/7266 (0%) 1 1/7274 (0%) 1
    Arterial haemorrhage 0/7266 (0%) 0 1/7274 (0%) 1
    Arteriovenous fistula 1/7266 (0%) 1 0/7274 (0%) 0
    Bleeding varicose vein 0/7266 (0%) 0 1/7274 (0%) 1
    Deep vein thrombosis 1/7266 (0%) 1 0/7274 (0%) 0
    Femoral artery aneurysm 0/7266 (0%) 0 1/7274 (0%) 1
    Haematoma 6/7266 (0.1%) 6 2/7274 (0%) 2
    Hypotension 1/7266 (0%) 1 0/7274 (0%) 0
    Intra-abdominal haematoma 0/7266 (0%) 0 1/7274 (0%) 1
    Lymphocele 1/7266 (0%) 1 0/7274 (0%) 0
    Lymphoedema 0/7266 (0%) 0 1/7274 (0%) 1
    Lymphorrhoea 1/7266 (0%) 1 0/7274 (0%) 0
    Temporal arteritis 1/7266 (0%) 1 0/7274 (0%) 0
    Varicose vein 0/7266 (0%) 0 1/7274 (0%) 1
    Other (Not Including Serious) Adverse Events
    Sitagliptin Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7266 (0%) 0/7274 (0%)

    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 at least 30 days prior to submission for publication/presentation or at least 14 calendar days prior to submission for abstracts.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00790205
    Other Study ID Numbers:
    • 0431-082
    • 2008_523
    • 2008-006719-20
    First Posted:
    Nov 13, 2008
    Last Update Posted:
    Nov 23, 2021
    Last Verified:
    Oct 1, 2021