Effect of Pioglitazone and Exenatide on Body Weight and Beta Cell Function
Condition: Type 2 Diabetes; Healthy; Impaired Glucose Tolerance
MeSH terms: Diabetes Mellitus, Type 2; Glucose Intolerance; Body Weight
Intervention: Pioglitazone; Exenatide; Pioglitazone and Exenatide
Intervention description: Pioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months; Exenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months; Pioglitazone 30mg daily for 1 month and then 45mg daily for 5 months and Exenatide 5mcg twice daily for one month then 10mcg twice daily for 5 months
Intervention MeSH terms: Pioglitazone; Exenatide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Type 2 diabetes pathogenesis, thiazolidinediones; impaired glucose tolerance; Incretins; Insulin secretion

Summary:

      Pioglitazone, a drug used in treatment of type 2 diabetes has been shown to improve insulin
      sensitivity in skeletal muscle, liver, and fat cells. Despite the beneficial effects of
      pioglitazone to improve insulin sensitivity and reduce cardiovascular disease in high risk
      type 2 diabetic patients, weight gain has been a limiting factor. Exenatide, another agent
      used for treatment of T2DM, improves glycemic control and promotes moderate weight loss. In
      this proposal we will examine the effect of combination therapy with pioglitazone plus
      exenatide on body weight, fat topography, beta cell function, glycemic control, and plasma
      lipid levels in subjects with type 2 diabetes mellitus compared to treatment with each drug
      separately. Assessment of beta cell function will be performed by measuring the maximal
      insulin secretory capacity using a maximal hyperglycemic stimulus combined with an
      intravenous arginine stimulus.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diabetic patients must be on diet therapy alone or diet plus a sulfonylurea, or diet
             plus metformin, or diet plus sulfonylurea/metformin and have a HbA1c ≥ 7.0%.

          2. Patients must have the following laboratory values:

             Hematocrit ≥ 34 vol% Serum creatinine ≤ 1.8 mg/dl AST (SGOT) ≤ 2 times upper limit of
             normal ALT (SGPT) ≤ 2 times upper limit of normal Alkaline phosphatase ≤ 2 times upper
             limit of normal

          3. Patients must have been on a stable dose of allowed chronic medications for 30 days
             prior to entering the study.

          4. Body weight must be stable (± 3-4 pounds) over the three months prior to study

          5. The normal healthy control group will be age, weight (BMI), and gender matched with
             the diabetic group and must have a normal OGTT according to ADA criteria.

          6. Subjects with IFG/IGT will have a FPG (100-125mg/dl) and/or 2-h plasma glucose
             (140-199mg/dl) according to ADA criteria.

        Exclusion Criteria:

          1. Patients must not have type 1 diabetes.

          2. Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c >
             10.0%.

          3. Patients must not have received a thiazolidinedione or insulin for more than one week
             during the year prior to randomization.

          4. Patients with a history of clinically significant heart disease (New York Heart
             Classification greater than class 2.