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

Diabetes Clinical Trial

Official title: Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With Type 2 Diabetes Mellitus

Status Completed

Clinical Trial Summary

In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:

Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP).

Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.

Clinical Trial Description

PRIMARY:

In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:

Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP).

Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.

SECONDARY:

In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:

1. Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on post-meal glucose during meal tolerance test (MTT).

Hypothesis: After 6 weeks of treatment the co-administration of sitagliptin and metformin provides greater reduction in the total glucose AUC (0-6 hr) during MTT compared to placebo.

2. Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on fasting plasma glucose (FPG).

Hypothesis: After 6 weeks of treatment the co-administration of sitagliptin and metformin provides greater reduction in FPG compared to placebo.

3. Objective: To assess the effects sitagliptin alone compared to placebo on HGP. Hypothesis: After 6 weeks of treatment, sitagliptin alone provides greater reduction in HGP compared to placebo

EXPLORATORY OBJECTIVES:

(i) Objective: after 6 weeks of treatment, to assess the effects co-administration of sitagliptin and metformin compared to placebo on:

1. active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).

2. glucagon concentration (fasting and post-meal).

3. parameters of insulin secretion and insulin sensitivity.

4. splanchnic glucose uptake.

(ii) Objective: after 6 weeks of treatment, to assess the effects co-administration of sitagliptin and metformin compared to treatment with sitagliptin alone and metformin alone on:

5. glucose concentration (fasting and total glucose AUC [0-6 hr]).

6. active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).

7. glucagon concentration (fasting and post-meal).

8. parameters of insulin secretion and insulin sensitivity.

9. HGP.

10. splanchnic glucose uptake. (iii) Objective: after 6 weeks of treatment, to assess the effects of sitagliptin alone and metformin alone compared to placebo on:

11. glucose concentration (fasting and total glucose AUC [0-6 hr]).

12. active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).

13. glucagon concentration (fasting and post-meal).

14. parameters of insulin secretion and insulin sensitivity.

15. HGP.

16. splanchnic glucose uptake. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes

• NCT number: NCT00820573
• Study type: Interventional
• Source: The University of Texas Health Science Center at San Antonio
• Status: Completed
• Phase: Phase 4
• Start date: October 2009
• Completion date: October 2012