Trial Outcomes & Findings for Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM (NCT NCT00820573)

Results Overview

Baseline endogenous glucose production prior to a mixed meal tolerance test (placebo) and following 6 weeks of either sitagliptin, metformin or sitagliptin plus metformin combination therapy in all 16 participants

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

16 participants

Primary outcome timeframe

6 weeks

Results posted on

2013-12-13

Participant Flow

Texas Diabetes Institute from March 2010 July 2011

A 4 week washout period for those subjects on oral anti-diabetic therapy with sulfonylureas was used in 7 subjects

Participant milestones

Participant milestones
Measure	Placebo,Sitagliptin,Metformin and Sitagliptin Plus Metformin Sequence as described, starting placebo therapy for 6 weeks,followed by sitagliptin 100 mg once daily, then metformin 1000 mg twice daily for 6 weeks and the combination sitagliptn plus metformin for the final 6 weeks	Sitagliptin, Metformin, Sitagliptin Plus Metformin, Placebo Sequence as described, starting with sitagliptin 100 mg once daily, then metformin 1000 mg twice daily for 6 weeks, combination sitagliptn plus metformin for 6 weeks and then placebo therapy for the final 6 weeks	Metformin, Sitagliptin Plus Metformin, Sitagliptin,Placebo Sequence as described, starting with metformin 1000 mg twice daily for 6 weeks, combination sitagliptn plus metformin for 6 weeks, then sitagliptin 100 mg daily followed by placebo therapy for the final 6 weeks	Sitagliptin Plus Metformin, Sitagliptin, Placebo,Metformin Sequence as described, starting with combination sitagliptn plus metformin for 6 weeks, then sitagliptin 100 mg daily placebo therapy for 6 weeks and finally metforminfor 6 weeks.
Overall Study STARTED	4	4	4	4
Overall Study COMPLETED	4	4	4	4
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=4 Participants all subjects after 6 weeks of placebo therapy	Metformin n=4 Participants all subjects after receiving 6 weeks of metformin therapy	Sitagliptin n=4 Participants all subjects after receiving 6 weeks of sitagliptin therapy	Metformin Plus Sitagliptin n=4 Participants all subjects after receiving 6 weeks of combined sitagliptin plus metformin therpay	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	4 Participants n=483 Participants	16 Participants n=36 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	6 Participants n=36 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	10 Participants n=36 Participants
Region of Enrollment United States	4 participants n=93 Participants	4 participants n=4 Participants	4 participants n=27 Participants	4 participants n=483 Participants	16 participants n=36 Participants

PRIMARY outcome

Timeframe: 6 weeks

Baseline endogenous glucose production prior to a mixed meal tolerance test (placebo) and following 6 weeks of either sitagliptin, metformin or sitagliptin plus metformin combination therapy in all 16 participants

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin Plus Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order
Objective: Comparisons of the Effects of Co-administration of Sitagliptin and Metformin Alone or in Combination Versus Placebo on Baseline Endogenous Glucose Production (EGP).	2.0 mg/kg.min Standard Error 0.2	1.8 mg/kg.min Standard Error 0.2	1.7 mg/kg.min Standard Error 0.2	1.5 mg/kg.min Standard Error 0.1

PRIMARY outcome

Timeframe: 6 weeks

Population: power calculations with data from previous similar studies

The degree of suppression of baseline endogenous glucose production was measured in absolute values and as a percent of basal values at the end of each 6-week therapeutic period. The absolute values obtained in each sequence study group (both basal and post-meal) were compared amongst all groups.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin Plus Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order
Average of Plasma Glucose During Mixed Meal Tolerance Test (MTT) Compared to Baseline Plasma Glucose to Post Therapy (6-weeks).	1.8 mg/kg.min Standard Error 0.2	1.6 mg/kg.min Standard Error 0.2	1.7 mg/kg.min Standard Error 0.2	1.5 mg/kg.min Standard Error 0.2

SECONDARY outcome

Timeframe: 6 weeks

Population: All 16 participants were analyzed using ANOVA to compare results after each 6 week period of exposure to therapeutic agent(s)

Basal pasma glucose was determined with the glucose oxidase method after each specific 6 week treatment. The absolute values obtained of basal plasma glucose at the end of each 6-week therapeutic period in each sequence study group (both basal and post-meal) were compared amongst all groups.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin Plus Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order
Fasting Plasma Glucose 6 Weeks After Therapy	160 mg/dl Standard Error 4	145 mg/dl Standard Error 5	150 mg/dl Standard Error 4	120 mg/dl Standard Error 6

SECONDARY outcome

Timeframe: 360 min

Population: power calculation based on previous data

The absolute values of mean plasma glucose post-meal (360 minutes)were determined after each specific 6 week treatment and these absolute values after each specific sequence therapy were compared amongst all groups.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order	Sitagliptin Plus Metformin n=16 Participants All participants received placebo, metformin, sitagliptin and the combination therapy for 6 weeks in random order
Changes in Plasma Glucose Post-MTT After Each Six Weeks of Therapy Compared to Baseline	205 mg/dl Standard Error 5	191 mg/dl Standard Error 4	195 mg/dl Standard Error 4	161 mg/dl Standard Error 3

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Metformin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Metformin Plus Sitagliptin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Eugenio Cersosimo, MD PhD

University of Texas HSC at San Antonio

Phone: 210 358 7200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place