Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Sitagliptin 100 mg in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control (MK-0431-229) (NCT NCT01076075)

Last Updated: 2017-06-05

Results Overview

Change from baseline reflects the Week 24 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

427 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2017-06-05

Participant Flow

762 participants were screened, 335 participants were excluded, and 427 participants were randomized. There was a single-blind run-in prior to randomization.

Participant milestones

Participant milestones
Measure	Sitagliptin Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + Placebo to Pioglitazone	Placebo/Pioglitazone Phase A (Weeks 0-24): Placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): Placebo to Sitagliptin 100 mg + Pioglitazone 30 mg
Overall Study STARTED	213	214
Overall Study Completed Phase A	199	189
Overall Study COMPLETED	172	167
Overall Study NOT COMPLETED	41	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + Placebo to Pioglitazone	Placebo/Pioglitazone Phase A (Weeks 0-24): Placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): Placebo to Sitagliptin 100 mg + Pioglitazone 30 mg
Overall Study Adverse Event	3	9
Overall Study Lack of Efficacy	5	4
Overall Study Lost to Follow-up	6	5
Overall Study other	19	9
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	8	19

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of Sitagliptin 100 mg in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control (MK-0431-229)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=210 Participants Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + Placebo to Pioglitazone	Placebo/Pioglitazone n=212 Participants Phase A (Weeks 0-24): Placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): Placebo to Sitagliptin 100 mg + Pioglitazone 30 mg	Total n=422 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 9.6 • n=5 Participants	55.4 years STANDARD_DEVIATION 10.2 • n=7 Participants	54.9 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	115 Participants n=5 Participants	114 Participants n=7 Participants	229 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	98 Participants n=7 Participants	193 Participants n=5 Participants
Hemoglobin A1C	8.4 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.4 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	8.4 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants
2-Hour Post-Meal Glucose	240.3 mg/dL STANDARD_DEVIATION 60.6 • n=5 Participants	243.3 mg/dL STANDARD_DEVIATION 68.8 • n=7 Participants	241.8 mg/dL STANDARD_DEVIATION 64.8 • n=5 Participants
Fasting Plasma Glucose	164.8 mg/dL STANDARD_DEVIATION 40.8 • n=5 Participants	165.0 mg/dL STANDARD_DEVIATION 43.9 • n=7 Participants	164.9 mg/dL STANDARD_DEVIATION 42.4 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The Full Analysis Set Population received at least one dose of study treatment and had baseline data and at least one post-baseline treatment endpoint observation for the analysis endpoint. Missing data were imputed using last observation carried forward (LOCF). Five participants were excluded from analyses due to one site's non-compliance.

Change from baseline reflects the Week 24 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.

Outcome measures

Outcome measures
Measure	Sitagliptin n=203 Participants Phase A (Weeks 0-24): Sitagliptin 100 mg	Placebo/Pioglitazone n=202 Participants Phase A (Week 0-24): Placebo to Sitagliptin 100 mg
Change From Baseline in Hemoglobin A1C (%) at Week 24	-0.84 Percentage of glycosylated hemoglobin 95% Confidence Interval 0.82 • Interval -0.97 to -0.71	-0.16 Percentage of glycosylated hemoglobin 95% Confidence Interval 0.84 • Interval -0.28 to -0.03

PRIMARY outcome

Timeframe: Week 0 to Week 54

Population: The All Patients as Treated Population took at least one dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Adverse events include those that occurred prior to a receiving rescue medication. Five participants were excluded from analyses due to 1 site's non-compliance.

Outcome measures

Outcome measures
Measure	Sitagliptin n=210 Participants Phase A (Weeks 0-24): Sitagliptin 100 mg	Placebo/Pioglitazone n=212 Participants Phase A (Week 0-24): Placebo to Sitagliptin 100 mg
Number of Participants With One or More Adverse Events (AEs) - Week 0 to Week 54	120 participants	122 participants

PRIMARY outcome

Timeframe: Week 0 to Week 54

Population: The All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Participants discontinued due to adverse events are reported regardless of rescue medication. Five participants were excluded from analyses due to 1 site's non-compliance.

Outcome measures

Outcome measures
Measure	Sitagliptin n=210 Participants Phase A (Weeks 0-24): Sitagliptin 100 mg	Placebo/Pioglitazone n=212 Participants Phase A (Week 0-24): Placebo to Sitagliptin 100 mg
Number of Participants Discontinuing Study Drug Due to An Adverse Event	3 participants	9 participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Change from baseline reflects the Week 24 value minus the baseline value. Two-hour post-meal glucose was measured following a standard meal.

Outcome measures

Outcome measures
Measure	Sitagliptin n=184 Participants Phase A (Weeks 0-24): Sitagliptin 100 mg	Placebo/Pioglitazone n=183 Participants Phase A (Week 0-24): Placebo to Sitagliptin 100 mg
Change From Baseline in 2-hour Post-Meal Glucose at Week 24	-36.8 mg/dL 95% Confidence Interval 60.8 • Interval -45.2 to -28.4	-3.3 mg/dL 95% Confidence Interval 67.8 • Interval -11.7 to 5.0

SECONDARY outcome

Timeframe: Baseline to Week 24

Change from baseline reflects the Week 24 value minus the baseline value.

Outcome measures

Outcome measures
Measure	Sitagliptin n=204 Participants Phase A (Weeks 0-24): Sitagliptin 100 mg	Placebo/Pioglitazone n=203 Participants Phase A (Week 0-24): Placebo to Sitagliptin 100 mg
Change From Baseline in Fasting Plasma Glucose at Week 24	-13.2 mg/dL Interval -18.8 to -7.7	5.3 mg/dL Interval -0.2 to 10.9

Adverse Events

Sitagliptin

Serious events: 6 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo/Pioglitazone

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sitagliptin n=210 participants at risk Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + Placebo to Pioglitazone	Placebo/Pioglitazone n=212 participants at risk Phase A (Weeks 0-24): Placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): Placebo to Sitagliptin 100 mg + Pioglitazone 30 mg
Infections and infestations Upper respiratory tract infection	6.7% 14/210 • Number of events 15 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	7.1% 15/212 • Number of events 16 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Metabolism and nutrition disorders Hypoglcaemia	18.1% 38/210 • Number of events 187 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	14.6% 31/212 • Number of events 148 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.

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 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sitagliptin n=210 participants at risk Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + Placebo to Pioglitazone	Placebo/Pioglitazone n=212 participants at risk Phase A (Weeks 0-24): Placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): Placebo to Sitagliptin 100 mg + Pioglitazone 30 mg
Cardiac disorders Angina pectoris	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Cardiac disorders Atrial flutter	0.48% 1/210 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.00% 0/212 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Hepatobiliary disorders Cholelithiasis	0.48% 1/210 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.00% 0/212 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Infections and infestations Abscess limb	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Infections and infestations Appendicitis	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Infections and infestations Cellulitis	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Infections and infestations Gangrene	0.48% 1/210 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.00% 0/212 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Infections and infestations Tooth abscess	0.48% 1/210 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.00% 0/212 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Infections and infestations Urosepsis	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Nervous system disorders Ischaemic stroke	0.48% 1/210 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.00% 0/212 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Renal and urinary disorders Bladder neck obstruction	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Renal and urinary disorders Renal colic	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.48% 1/210 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.00% 0/212 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.
Vascular disorders Hypertensive crisis	0.00% 0/210 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.	0.47% 1/212 • Number of events 1 • Week 0 to Week 54 All Patients as Treated Population took at least 1 dose of study drug. Participants received glycemic rescue medication if they met specific glycemic goals up to Week 24. Serious AEs (SAEs) are reported regardless of rescue medication. Other AEs are those that occurred prior to rescue medication. Five participants were excluded from analyses.