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Effect of Pioglitazone and Exenatide on Body Weight and Beta Cell Function (PIO-EX)

This study has been completed.
Sponsor:
Information provided by:
The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT00845182
First received: February 17, 2009
Last updated: July 21, 2010
Last verified: July 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Healthy Controls
Impaired Glucose Tolerance
 Drug: Pioglitazone
Drug: Exenatide
Drug: Pioglitazone and Exenatide
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Effect of Pioglitazone With and Without Exenatide on Body Weight, Fat Topography, Beta Cell Function, and Glycemic Control in Type 2 Diabetic Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Effect of Pioglitazone, Exenatide, and Pioglitazone plus Exenatide on Body weight, fat distribution, and beta cell function [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect pioglitazone, exenatide, and pioglitazone plus exenatide on • Insulin sensitivity • Inflammatory cytokines • glucagon and free fatty acids • plasma lipids [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: June 2007
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pioglitazone
Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm
 Drug: Pioglitazone
Pioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months
Other Name: ACTOS
Experimental: Exenatide
Exenatide: 15 subjects will be randomized to receive Exenatide
 Drug: Exenatide
Exenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months
Other Name: BYETTA
Experimental: Pioglitazone and Exentatide
Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide
 Drug: Pioglitazone and Exenatide
Pioglitazone 30mg daily for 1 month and then 45mg daily for 5 months Exenatide 5mcg twice daily for one month then 10mcg twice daily for 5 months
Other Names:
  • ACTOS
  • BYETTA

Detailed Description:

The thiazolidinedione (TZD) class of drugs has been shown to improve insulin sensitivity in skeletal muscle, liver, and adipocytes and to have anti-inflammatory and cardioprotective effects. The beta cell function, measured by the insulin secretion/insulin resistance index during the OGTT, improves significantly. In the present study, we will perform a more definitive assessment of beta cell function in TZD-treated diabetic patients by measuring the maximal insulin secretory capacity using a maximal hyperglycemic stimulus combined with an intravenous arginine stimulus.

Despite the beneficial effects of pioglitazone to improve insulin sensitivity and reduce cardiovascular events in high risk type 2 diabetic patients, weight gain has been a limiting factor for primary care physicians even though pioglitazone treatment leads to a redistribution of fat out of muscle/liver/visceral area to subcutaneous fat.

Exenatide (Byetta) is 39 amino acid peptide which exhibits biological actions similar to GLP-1. In clinical trials exenatide reduces HbA1c by 1-1.2% in subjects with type 2 diabetes and promotes moderate weight loss which is sustained for up to 2 years.

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 monotherapy with each agent separately. We postulate that combination therapy will result in significant weight loss (in contrast to the weight gain which accompanies pioglitazone treatment) and have an additive, or even synergistic, effect to improve beta cell function and glycemic control in type 2 diabetic patients who are inadequately controlled on oral agent therapy with metformin alone, a sulfonylurea alone, or combination of metformin plus a sulfonylurea. We will also compare the insulin secretion in healthy control subjects (NGT, n=15) and subjects with impaired glucose tolerance (IGT, n=15) to evaluate the relative decline in beta cell function in T2DM compared to NGT and IGT subjects. NGT and IGT subjects will participate only in a OGTT and a Hyperglycemic clamp- they will not receive any medication.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00845182

Locations
United States, Texas
Barter Research Center, ALM VA Hospital
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Investigators
Principal Investigator: Devjit Tripathy, MD University of Texas Health Science Center at San Antonio
  More Information

No publications provided

Responsible Party: Devjit Tripathy/Assistant Professor, Div of Diabetes, Dept of Medicine, University oif Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT00845182     History of Changes
Other Study ID Numbers: HSC2007243H
Study First Received: February 17, 2009
Last Updated: July 21, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at San Antonio:
Type 2 diabetes pathogenesis, thiazolidinediones
impaired glucose tolerance
Incretins
Insulin secretion

Additional relevant MeSH terms:
Body Weight
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Intolerance
Signs and Symptoms
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Hyperglycemia
Pioglitazone
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013