Trial Outcomes & Findings for Sitagliptin Cardiovascular Outcomes Study (MK-0431-082) (NCT NCT00790205)

Last Updated: 2021-11-23

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

14671 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2021-11-23

Participant Flow

A total of 14,671 participants were randomized to treatment, provided consent and did not have any Good Clinical Practice (GCP) deviations.

Participant milestones

Participant milestones
Measure	Sitagliptin Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Overall Study STARTED	7332	7339
Overall Study Treated	7266	7274
Overall Study COMPLETED	6972	6905
Overall Study NOT COMPLETED	360	434

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Overall Study Lost to Follow-up	61	71
Overall Study Withdrawal by Subject	299	363

Baseline Characteristics

Sitagliptin Cardiovascular Outcomes Study (MK-0431-082)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=7332 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7339 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years	Total n=14671 Participants Total of all reporting groups
Age, Customized Adults 18 - 64 years	3315 Participants 7.9 • n=5 Participants	3301 Participants 8.0 • n=7 Participants	65.5 Participants 8.0 • n=5 Participants
Age, Customized From 65 - 84 years	3813 Participants n=5 Participants	3821 Participants n=7 Participants	7634 Participants n=5 Participants
Age, Customized 85 years and over	46 Participants n=5 Participants	55 Participants n=7 Participants	101 Participants n=5 Participants
Age, Customized Unknown age	158 Participants n=5 Participants	162 Participants n=7 Participants	320 Participants n=5 Participants
Sex: Female, Male Female	2134 Participants n=5 Participants	2163 Participants n=7 Participants	4297 Participants n=5 Participants
Sex: Female, Male Male	5198 Participants n=5 Participants	5176 Participants n=7 Participants	10374 Participants n=5 Participants
Estimated Glomerular Filtration Rate (eGFR)	74.9 mL/min/1.73 m^2 STANDARD_DEVIATION 21.3 • n=5 Participants	74.9 mL/min/1.73 m^2 STANDARD_DEVIATION 20.9 • n=7 Participants	74.9 mL/min/1.73 m^2 STANDARD_DEVIATION 21.1 • n=5 Participants
Hemoglobin A1c (HbA1c)	7.2 Percentage of HbA1c STANDARD_DEVIATION 0.5 • n=5 Participants	7.2 Percentage of HbA1c STANDARD_DEVIATION 0.5 • n=7 Participants	7.2 Percentage of HbA1c STANDARD_DEVIATION 0.5 • n=5 Participants
Urine albumin creatinine ratio	8.6 g/mol Creatinine STANDARD_DEVIATION 37.4 • n=5 Participants	8.4 g/mol Creatinine STANDARD_DEVIATION 36.0 • n=7 Participants	8.5 g/mol Creatinine STANDARD_DEVIATION 36.7 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: 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.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7257 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7266 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)	9.6 Percentage of participants	9.6 Percentage of participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7332 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7339 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)	11.4 Percentage of participants	11.6 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7257 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7266 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)	8.4 Percentage of participants	8.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7332 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7339 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)	10.2 Percentage of participants	10.2 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7257 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7266 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percent Incidence of All-cause Mortality (Per Protocol Population)	4.7 Percentage of participants	4.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7332 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7339 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percent Incidence of All-cause Mortality (Intent to Treat Population)	7.5 Percentage of participants	7.3 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=7257 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7266 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)	2.8 Percentage of participants Interval 1.0 to 1.53	2.8 Percentage of participants Interval 0.84 to 1.33

SECONDARY outcome

Timeframe: Up to 5 years

Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7332 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7339 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)	3.1 Percentage of participants Interval 1.0 to 1.53	3.1 Percentage of participants Interval 0.84 to 1.33

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=7182 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7203 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 4; Sitagliptin, n= 3859; Placebo, n= 3864	-1.9 mL/min/1.73 m^2 Standard Deviation 14.2	-0.8 mL/min/1.73 m^2 Standard Deviation 14.3
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 8; Sitagliptin, n= 3562; Placebo, n= 3501	-2.5 mL/min/1.73 m^2 Standard Deviation 14.9	-0.9 mL/min/1.73 m^2 Standard Deviation 15.1
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 12; Sitagliptin, n=4912, Placebo, n=4778	-1.8 mL/min/1.73 m^2 Standard Deviation 15.8	-0.5 mL/min/1.73 m^2 Standard Deviation 16.2
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 24; Sitagliptin, n=4782, Placebo, n=4637	-3.1 mL/min/1.73 m^2 Standard Deviation 17.9	-1.7 mL/min/1.73 m^2 Standard Deviation 17.5
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 36; Sitagliptin, n=2776, Placebo, n=2614	-3.7 mL/min/1.73 m^2 Standard Deviation 18.0	-1.6 mL/min/1.73 m^2 Standard Deviation 18.8
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 48; Sitagliptin, n=1096, Placebo, n=1056	-3.7 mL/min/1.73 m^2 Standard Deviation 18.3	-2.8 mL/min/1.73 m^2 Standard Deviation 18.4
Change From Baseline in Renal Function Over Time (Per Protocol Population) Month 60; Sitagliptin, n=79, Placebo, n=88	-3.5 mL/min/1.73 m^2 Standard Deviation 18.2	-6.4 mL/min/1.73 m^2 Standard Deviation 17.3

SECONDARY outcome

Timeframe: Baseline and up to 5 years

Population: 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.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=7254 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7274 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 60; Sitagliptin, n=93; Placebo, n=106	-4.2 mL/min/1.73 m^2 Standard Deviation 17.4	-5.7 mL/min/1.73 m^2 Standard Deviation 17.2
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 4; Sitagliptin, n=3949; Placebo, n=3977	-1.8 mL/min/1.73 m^2 Standard Deviation 14.3	-0.8 mL/min/1.73 m^2 Standard Deviation 14.3
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 8; Sitagliptin, n=3687; Placebo, n=3648	-2.4 mL/min/1.73 m^2 Standard Deviation 14.8	-0.9 mL/min/1.73 m^2 Standard Deviation 15.2
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 12; Sitagliptin, n=5082; Placebo, n=5015	-1.8 mL/min/1.73 m^2 Standard Deviation 15.8	-0.5 mL/min/1.73 m^2 Standard Deviation 16.3
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 24; Sitagliptin, n=5157; Placebo, n=5071	-3.2 mL/min/1.73 m^2 Standard Deviation 17.9	-1.7 mL/min/1.73 m^2 Standard Deviation 17.7
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 36; Sitagliptin, n=3037; Placebo, n=2942	-3.8 mL/min/1.73 m^2 Standard Deviation 18.1	-1.6 mL/min/1.73 m^2 Standard Deviation 18.7
Change From Baseline in Renal Function Over Time (Intent to Treat Population) Month 48; Sitagliptin, n=1237; Placebo, n=1210	-4.0 mL/min/1.73 m^2 Standard Deviation 18.4	-2.8 mL/min/1.73 m^2 Standard Deviation 18.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=7250 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7258 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 4; Sitagliptin, n=6632, Placebo, n=6588	-0.3 Percentage of HbA1c Standard Deviation 0.8	0.1 Percentage of HbA1c Standard Deviation 0.9
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 8; Sitagliptin, n=6294, Placebo, n=6197	-0.3 Percentage of HbA1c Standard Deviation 0.9	0.1 Percentage of HbA1c Standard Deviation 1.0
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 12; Sitagliptin, n=6217, Placebo, n=6092	-0.2 Percentage of HbA1c Standard Deviation 1.0	0.1 Percentage of HbA1c Standard Deviation 1.0
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 24; Sitagliptin, n=5668, Placebo, n=5475	-0.1 Percentage of HbA1c Standard Deviation 1.0	0.2 Percentage of HbA1c Standard Deviation 1.1
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 36; Sitagliptin, n=3227, Placebo, n=3083	-0.1 Percentage of HbA1c Standard Deviation 1.1	0.1 Percentage of HbA1c Standard Deviation 1.1
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 48; Sitagliptin, n=1271, Placebo, n=1224	0.0 Percentage of HbA1c Standard Deviation 1.1	0.1 Percentage of HbA1c Standard Deviation 1.2
Change From Baseline in HbA1c Over Time (Per Protocol Population) Month 60; Sitagliptin, n=106, Placebo, n=108	-0.1 Percentage of HbA1c Standard Deviation 1.0	0.0 Percentage of HbA1c Standard Deviation 0.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sitagliptin n=7325 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7331 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 4: Sitagliptin, n= 6772; Placebo, n= 6738	-0.3 Percentage of HbA1c Standard Deviation 0.8	0.1 Percentage of HbA1c Standard Deviation 0.9
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 8: Sitagliptin, n= 6478; Placebo, n= 6414	-0.2 Percentage of HbA1c Standard Deviation 0.9	0.1 Percentage of HbA1c Standard Deviation 1.0
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 12: Sitagliptin, n= 6448; Placebo, n= 6384	-0.2 Percentage of HbA1c Standard Deviation 1.0	0.1 Percentage of HbA1c Standard Deviation 1.0
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 24: Sitagliptin, n= 6105; Placebo, n= 5975	-0.1 Percentage of HbA1c Standard Deviation 1.0	0.1 Percentage of HbA1c Standard Deviation 1.1
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 36: Sitagliptin, n= 3521; Placebo, n= 3439	-0.1 Percentage of HbA1c Standard Deviation 1.1	0.1 Percentage of HbA1c Standard Deviation 1.1
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 48: Sitagliptin, n= 1432; Placebo, n= 1383	0.0 Percentage of HbA1c Standard Deviation 1.1	0.1 Percentage of HbA1c Standard Deviation 1.2
Change From Baseline in HbA1c Over Time (Intent to Treat Population) Month 60: Sitagliptin, n= 123; Placebo, n= 128	0.0 Percentage of HbA1c Standard Deviation 1.0	0.0 Percentage of HbA1c Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline and up to 5 years

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=2590 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=2522 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 4; Sitagliptin, n=664; Placebo, n=688	-2.2 g/mol Creatinine Standard Deviation 27.7	-1.4 g/mol Creatinine Standard Deviation 24.6
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 8; Sitagliptin, n=635; Placebo, n=597	1.7 g/mol Creatinine Standard Deviation 38.5	0.2 g/mol Creatinine Standard Deviation 45.3
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 12; Sitagliptin, n=1126; Placebo, n=1059	0.8 g/mol Creatinine Standard Deviation 27.7	1.2 g/mol Creatinine Standard Deviation 33.1
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 24; Sitagliptin, n=930; Placebo, n=892	0.7 g/mol Creatinine Standard Deviation 34.0	3.2 g/mol Creatinine Standard Deviation 31.6
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 36; Sitagliptin, n=488; Placebo, n=513	2.5 g/mol Creatinine Standard Deviation 24.0	4.0 g/mol Creatinine Standard Deviation 31.0
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 48; Sitagliptin, n=238; Placebo, n=233	1.3 g/mol Creatinine Standard Deviation 15.2	1.5 g/mol Creatinine Standard Deviation 25.5
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) Month 60; Sitagliptin, n=13; Placebo, n=17	-2.7 g/mol Creatinine Standard Deviation 10.1	4.8 g/mol Creatinine Standard Deviation 15.4

SECONDARY outcome

Timeframe: Baseline and up to 5 years

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=2606 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=2542 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 4; n=677, n=713	-2.1 g/mol Creatinine Standard Deviation 27.5	-1.4 g/mol Creatinine Standard Deviation 24.1
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 8; n=658, n=624	2.1 g/mol Creatinine Standard Deviation 39.4	0.5 g/mol Creatinine Standard Deviation 44.5
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 12; n=1167, n=1115	1.3 g/mol Creatinine Standard Deviation 30.2	1.2 g/mol Creatinine Standard Deviation 32.3
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 24; n=1011, n=964	0.5 g/mol Creatinine Standard Deviation 33.1	3.1 g/mol Creatinine Standard Deviation 30.7
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 36; n=537, n=553	2.6 g/mol Creatinine Standard Deviation 25.8	3.9 g/mol Creatinine Standard Deviation 30.3
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 48; n=265, n=256	1.9 g/mol Creatinine Standard Deviation 16.3	1.6 g/mol Creatinine Standard Deviation 24.5
Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) Month 60; n=14, n=18	-2.5 g/mol Creatinine Standard Deviation 9.7	6.4 g/mol Creatinine Standard Deviation 16.4

SECONDARY outcome

Timeframe: Up to 5 years

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=5554 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=5601 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)	8.6 Percentage of participants	11.9 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=5608 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=5655 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)	9.7 Percentage of participants	13.2 Percentage of participants

SECONDARY outcome

Timeframe: 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.)

Outcome measures

Outcome measures
Measure	Sitagliptin n=7257 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7266 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)	18.9 Percentage of participants	24.5 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: Intent to treat population included all randomized participants who received study medication, provided consent, and did not have a major GCP deviation.

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.)

Outcome measures

Outcome measures
Measure	Sitagliptin n=7332 Participants Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7339 Participants Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)	21.7 Percentage of participants	27.9 Percentage of participants

Adverse Events

Sitagliptin

Serious events: 928 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 909 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Sitagliptin n=7266 participants at risk Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years	Placebo n=7274 participants at risk Matching placebo tablet taken orally once daily in the morning for up to approximately 5 years
Cardiac disorders Bradycardia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Metabolism and nutrition disorders Obesity	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Ankle impingement	0.03% 2/7266 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.03% 2/7266 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Atrioventricular block	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	0.32% 23/7266 • Number of events 24 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.32% 23/7274 • Number of events 23 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia vitamin B12 deficiency	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Haemolytic anaemia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Iron deficiency anaemia	0.08% 6/7266 • Number of events 6 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.08% 6/7274 • Number of events 6 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Lymphadenopathy mediastinal	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Microcytic anaemia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Pernicious anaemia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Cor pulmonale	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Coronary artery thrombosis	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Palpitations	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Pericardial effusion	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Cardiac disorders Sinus arrhythmia	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Arteriovenous malformation	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Hamartoma	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Hydrocele	0.03% 2/7266 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Phimosis	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Pyloric stenosis	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.03% 2/7274 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Syringomyelia	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.03% 2/7274 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Vitello-intestinal duct remnant	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Deafness bilateral	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Hypoacusis	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Meniere's disease	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Sudden hearing loss	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Tinnitus	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	0.06% 4/7266 • Number of events 4 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.03% 2/7274 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo labyrinthine	0.00% 0/7266 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo positional	0.04% 3/7266 • Number of events 3 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.03% 2/7274 • Number of events 2 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Ear and labyrinth disorders Vestibular disorder	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.01% 1/7274 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.
Endocrine disorders Adrenocortical insufficiency acute	0.01% 1/7266 • Number of events 1 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.	0.00% 0/7274 • Up to 68 months (including up to 28 days after last dose of study drug) All participants as treated (APaT) population includes participants who received at least one dose of study drug.