Trial Outcomes & Findings for Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus (0431-061) (NCT NCT00511108)

Last Updated: 2017-05-12

Results Overview

Glucagon concentration was measured at 9 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, and 180 minutes. Total AUC was calculated over 3 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

211 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2017-05-12

Participant Flow

First Patient In: 12-Sep-2007; Last Patient Last Visit: 24-Feb-2009 Forty-four medical clinics worldwide (17 in the United States, 20 in Europe, 4 in Australia, and 3 in Israel).

Patients 30-65 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control (fasting plasma glucose \[FPG\] 130-260 mg/dL \[7.2-14.4 mmol/L\]) on diet and exercise alone were eligible for randomization.

Participant milestones

Participant milestones
Measure	Sitagliptin 100 mg Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Overall Study STARTED	52	54	52	53
Overall Study COMPLETED	46	52	47	48
Overall Study NOT COMPLETED	6	2	5	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin 100 mg Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Overall Study Adverse Event	2	0	1	2
Overall Study Lost to Follow-up	0	2	1	0
Overall Study Physician Decision	0	0	0	1
Overall Study Withdrawal by Subject	4	0	3	2

Baseline Characteristics

Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus (0431-061)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin 100 mg n=52 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg n=54 Participants Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg n=52 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo n=53 Participants Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Total n=211 Participants Total of all reporting groups
Age, Continuous	54.6 years STANDARD_DEVIATION 7.6 • n=5 Participants	53.4 years STANDARD_DEVIATION 7.8 • n=7 Participants	53.3 years STANDARD_DEVIATION 8.6 • n=5 Participants	53.3 years STANDARD_DEVIATION 7.7 • n=4 Participants	53.6 years STANDARD_DEVIATION 7.9 • n=21 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	31 Participants n=7 Participants	18 Participants n=5 Participants	21 Participants n=4 Participants	94 Participants n=21 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	23 Participants n=7 Participants	34 Participants n=5 Participants	32 Participants n=4 Participants	117 Participants n=21 Participants
Race/Ethnicity, Customized White	45 participants n=5 Participants	43 participants n=7 Participants	49 participants n=5 Participants	48 participants n=4 Participants	185 participants n=21 Participants
Race/Ethnicity, Customized Black	6 participants n=5 Participants	9 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	20 participants n=21 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	4 participants n=21 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Glucose 5-hour (hr) Total area under the curve (AUC)	1179.9 mg*hr/dL STANDARD_DEVIATION 322.8 • n=5 Participants	1250.6 mg*hr/dL STANDARD_DEVIATION 349.6 • n=7 Participants	1276.0 mg*hr/dL STANDARD_DEVIATION 348.5 • n=5 Participants	1255.1 mg*hr/dL STANDARD_DEVIATION 290.9 • n=4 Participants	1240.4 mg*hr/dL STANDARD_DEVIATION 328.4 • n=21 Participants
Hemoglobin A1c (HbA1c)	7.7 Percent STANDARD_DEVIATION 0.8 • n=5 Participants	7.9 Percent STANDARD_DEVIATION 0.9 • n=7 Participants	7.9 Percent STANDARD_DEVIATION 0.9 • n=5 Participants	8.0 Percent STANDARD_DEVIATION 1.1 • n=4 Participants	7.9 Percent STANDARD_DEVIATION 1.0 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. For FAS patients with no data at Week 12, the last observed measurement was carried forward to Week 12.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=48 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg n=47 Participants Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg n=42 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo n=39 Participants Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment	-17.2 pg*hr/mL Interval -30.1 to -4.2	-4.9 pg*hr/mL Interval -18.1 to 8.3	-29.8 pg*hr/mL Interval -43.6 to -16.1	12.5 pg*hr/mL Interval -1.9 to 26.9

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Static sensitivity is a measure of the effect of glucose on beta cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. Percent change from baseline was calculated as the difference between index of static sensitivities at Week 12 and at baseline with respect to the index of static sensitivity at baseline times 100.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=38 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg n=34 Participants Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg n=27 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo n=33 Participants Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment	71.5 Percent Change Interval 46.8 to 100.3	27.0 Percent Change Interval 7.8 to 49.7	125.2 Percent Change Interval 87.2 to 171.0	-2.3 Percent Change Interval -17.4 to 15.5

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Glucose concentration was measured at 11 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, 180, 240, 300 minutes. Total AUC was calculated over 5 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=48 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg n=49 Participants Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg n=44 Participants Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo n=42 Participants Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment	-209.8 mg*hr/dL Interval -281.6 to -138.0	-245.6 mg*hr/dL Interval -316.6 to -174.6	-389.2 mg*hr/dL Interval -463.6 to -314.7	18.6 mg*hr/dL Interval -58.2 to 95.4

Adverse Events

Sitagliptin 100 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Pioglitazone 30 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sitagliptin 100 mg + Pioglitazone 30 mg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin 100 mg n=52 participants at risk Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg n=54 participants at risk Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg n=52 participants at risk Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo n=53 participants at risk Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/52 • Weeks 0-12	0.00% 0/54 • Weeks 0-12	1.9% 1/52 • Weeks 0-12	0.00% 0/53 • Weeks 0-12
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.9% 1/52 • Weeks 0-12	0.00% 0/54 • Weeks 0-12	0.00% 0/52 • Weeks 0-12	0.00% 0/53 • Weeks 0-12

Other adverse events

Other adverse events
Measure	Sitagliptin 100 mg n=52 participants at risk Includes patients receiving once-daily administration of sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.	Pioglitazone 30 mg n=54 participants at risk Includes patients receiving once-daily administration of pioglitazone 30 mg and matching placebo to sitagliptin 100 mg.	Sitagliptin 100 mg + Pioglitazone 30 mg n=52 participants at risk Includes patients receiving once-daily administration of sitagliptin 100 mg and pioglitazone 30 mg.	Placebo n=53 participants at risk Includes patients receiving once-daily administration of matching placebo to sitagliptin 100 mg and matching placebo to pioglitazone 30 mg.
Infections and infestations Upper respiratory tract infection	0.00% 0/52 • Weeks 0-12	5.6% 3/54 • Weeks 0-12	0.00% 0/52 • Weeks 0-12	5.7% 3/53 • Weeks 0-12
Investigations Blood glucose increased	0.00% 0/52 • Weeks 0-12	0.00% 0/54 • Weeks 0-12	0.00% 0/52 • Weeks 0-12	5.7% 3/53 • Weeks 0-12
Metabolism and nutrition disorders Hyperglycaemia	5.8% 3/52 • Weeks 0-12	0.00% 0/54 • Weeks 0-12	0.00% 0/52 • Weeks 0-12	0.00% 0/53 • Weeks 0-12
Nervous system disorders Headache	0.00% 0/52 • Weeks 0-12	0.00% 0/54 • Weeks 0-12	0.00% 0/52 • Weeks 0-12	5.7% 3/53 • Weeks 0-12

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER