Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

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.
    

Detailed 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.
    

Intervention name(s): Sitagliptin; Metformin; Sitagliptin + Metformin; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): tablet, 100 mg/day, 6 weeks; tablet, 1000 mg/ bid, 6 weeks; tablet, Sitagliptin (100mg/day) + tablet, Metformin (1000 mg/bid), 6 weeks; Placebo 6 weeks
Other intervention name(s): Januvia; Glucophage; Januvia and glucophage; Placebo tablet
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Diabetes