Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Sitagliptin and MK0431A in Comparison to a Commonly Used Medication in Patients With Type 2 Diabetes (0431-068)(COMPLETED) (NCT NCT00541450)

Last Updated: 2017-05-12

Results Overview

The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

492 participants

Primary outcome timeframe

Baseline to 40 weeks

Results posted on

2017-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	Sita/Met FDC In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Phase A STARTED	244	248
Phase A COMPLETED	224	231
Phase A NOT COMPLETED	20	17
Phase B STARTED	224	231
Phase B COMPLETED	187	200
Phase B NOT COMPLETED	37	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Sita/Met FDC In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Phase A Adverse Event	3	0
Phase A Creatinine/CrCl -Increase in creatinine	0	2
Phase A Hyperglycemia	0	1
Phase A Lost to Follow-up	6	4
Phase A Physician Decision	2	0
Phase A Protocol Violation	2	3
Phase A Withdrawal by Subject	7	7
Phase B Adverse Event	6	6
Phase B Hyperglycemia	10	9
Phase B Lost to Follow-up	6	4
Phase B Physician Decision	4	2
Phase B Pregnancy	0	1
Phase B Protocol Violation	3	3
Phase B Withdrawal by Subject	8	6

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Sitagliptin and MK0431A in Comparison to a Commonly Used Medication in Patients With Type 2 Diabetes (0431-068)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sita/Met FDC n=244 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=248 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).	Total n=492 Participants Total of all reporting groups
Age, Continuous	50.5 years STANDARD_DEVIATION 10.9 • n=5 Participants	51.7 years STANDARD_DEVIATION 10.1 • n=7 Participants	51.1 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	92 Participants n=5 Participants	100 Participants n=7 Participants	192 Participants n=5 Participants
Sex: Female, Male Male	152 Participants n=5 Participants	148 Participants n=7 Participants	300 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 40 weeks

Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12, and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 (Phase A and Phase B); and (2) had a baseline measurement and at least one on-treatment measurement for A1C.

The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=218 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=222 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks	-1.75 percentage of glycosylated hemoglobin Interval -1.92 to -1.59	-1.38 percentage of glycosylated hemoglobin Interval -1.55 to -1.21

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12; and (2) had a baseline measurement and at least one on-treatment measurement for A1C.

The change in A1C compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. A1c represents percentage of glycosylated hemoglobin.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=231 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=240 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks	-1.03 percentage of glycosylated hemoglobin Interval -1.18 to -0.88	-0.87 percentage of glycosylated hemoglobin Interval -1.02 to -0.72

SECONDARY outcome

Timeframe: Baseline and 40 weeks

The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the Sita/Met FDC and the pioglitazone groups at Week 40.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=165 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=172 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks	-90.3 mg/dL Interval -99.6 to -81.0	-69.1 mg/dL Interval -78.2 to -60.0

SECONDARY outcome

Timeframe: Baseline to 12 weeks

The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the participants treated with Sitagliptin or Pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=202 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=210 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks	-52.8 mg/dL Interval -62.4 to -43.3	-50.1 mg/dL Interval -59.4 to -40.7

SECONDARY outcome

Timeframe: Baseline and 40 weeks

The change in FPG compared to baseline was measured for the Sita/Met FDC and the pioglitazone groups at Week 40.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=219 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=226 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks	-45.8 mg/dL Interval -51.1 to -40.5	-37.6 mg/dL Interval -42.8 to -32.4

SECONDARY outcome

Timeframe: Baseline to 12 weeks

The change in FPG compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=235 Participants In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone n=245 Participants In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone. In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.).
Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks	-26.6 mg/dL Interval -31.7 to -21.5	-28.0 mg/dL Interval -33.0 to -23.0

Adverse Events

Sitagliptin (Weeks 0-12)

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Pioglitazone (Weeks 0-12)

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Sita/Met FDC (Weeks 0-40)

Serious events: 8 serious events

Other events: 20 other events

Deaths: 0 deaths

Pioglitazone (Weeks 0-40)

Serious events: 3 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin (Weeks 0-12) n=244 participants at risk In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg q.d. of sitagliptin or matching placebo to pioglitazone.	Pioglitazone (Weeks 0-12) n=248 participants at risk In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone or matching placebo to sitagliptin. At Week 6, all participants were up-titrated to 30 mg q.d. pioglitazone.	Sita/Met FDC (Weeks 0-40) n=222 participants at risk In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg q.d. of sitagliptin or matching placebo to pioglitazone. In Phase B (Treatment Week 12-Week 40), participants were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg b.i.d., which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone (Weeks 0-40) n=230 participants at risk In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone or matching placebo to sitagliptin. At Week 6, participants were up-titrated to 30 mg q.d. In Phase B (Treatment Week 12 -Week 40), participants were administered 45 mg q.d.
Cardiac disorders Angina pectoris	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Cardiac disorders Atrial fibrillation	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/222 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.43% 1/230 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Cardiac disorders Myocardial infarction	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Gastrointestinal disorders Inguinal hernia	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
General disorders Sudden cardiac death	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Infections and infestations Gastroenteritis	0.41% 1/244 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Infections and infestations Infection parasitic	0.41% 1/244 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/222 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Injury, poisoning and procedural complications Eye injury	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Nervous system disorders Syncope	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/222 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.43% 1/230 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.40% 1/248 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/222 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.43% 1/230 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Reproductive system and breast disorders Prostatitis	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.45% 1/222 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Vascular disorders Arterial thrombosis limb	0.41% 1/244 • Number of events 1 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/248 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/222 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.00% 0/230 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.

Other adverse events

Other adverse events
Measure	Sitagliptin (Weeks 0-12) n=244 participants at risk In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg q.d. of sitagliptin or matching placebo to pioglitazone.	Pioglitazone (Weeks 0-12) n=248 participants at risk In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone or matching placebo to sitagliptin. At Week 6, all participants were up-titrated to 30 mg q.d. pioglitazone.	Sita/Met FDC (Weeks 0-40) n=222 participants at risk In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg q.d. of sitagliptin or matching placebo to pioglitazone. In Phase B (Treatment Week 12-Week 40), participants were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg b.i.d., which was increased to 50/1000 mg b.i.d. over a period of 4 weeks.	Pioglitazone (Weeks 0-40) n=230 participants at risk In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone or matching placebo to sitagliptin. At Week 6, participants were up-titrated to 30 mg q.d. In Phase B (Treatment Week 12 -Week 40), participants were administered 45 mg q.d.
General disorders Oedema peripheral	0.00% 0/244 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	2.8% 7/248 • Number of events 7 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	0.90% 2/222 • Number of events 2 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	5.7% 13/230 • Number of events 15 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Infections and infestations Nasopharyngitis	1.6% 4/244 • Number of events 4 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	2.4% 6/248 • Number of events 6 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	5.4% 12/222 • Number of events 14 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	5.2% 12/230 • Number of events 17 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.
Nervous system disorders Headache	1.6% 4/244 • Number of events 4 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	1.6% 4/248 • Number of events 4 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	4.1% 9/222 • Number of events 13 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.	5.2% 12/230 • Number of events 16 Participants that received at least one dose of study medication, which was sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12 and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 were analyzed. The analyses for Week 0-40 did not include participants who discontinued from the study during Weeks 0-12.

Additional Information

Vice President of Late Stage Development

Merck Sharp & Dohme Corp

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on the PI is that an investigator and/or his/her colleagues may publish the results for their study site independently subsequent to the multicenter publication, or 24 months after completion of the study, whichever comes first. The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review.
Publication restrictions are in place

Restriction type: OTHER