Effect of Pioglitazone and Exenatide on Body Weight and Beta Cell Function - Full Text View

Sponsor:	The University of Texas Health Science Center at San Antonio
Information provided by:	The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:	NCT00845182

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 IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Efficacy Study
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:

MedlinePlus related topics: Diabetes

Drug Information available for: Pioglitazone Pioglitazone hydrochloride Exenatide

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
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Pioglitazone: Active Comparator 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
Exenatide: Experimental 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
Pioglitazone and Exentatide: Experimental 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

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:

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%.
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
Patients must have been on a stable dose of allowed chronic medications for 30 days prior to entering the study.
Body weight must be stable (± 3-4 pounds) over the three months prior to study
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.
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:

Patients must not have type 1 diabetes.
Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c > 10.0%.
Patients must not have received a thiazolidinedione or insulin for more than one week during the year prior to randomization.
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

Contacts

Contact: Devjit Tripathy, MD	210-5676691	tripathy@uthscsa.edu
Contact: Ralph A DeFronzo, MD	210-5676691	albarado@uthscsa.edu

Locations

United States, Texas
Barter Research Center, ALM VA Hospital	Recruiting
San Antonio, Texas, United States, 78229
Contact: Devjit Tripathy, MD 210-567-6691 tripathy@uthscsa.edu
Contact: Ralph A DeFronzo, MD 210-5676691 albarado@uthscsa.edu
Principal Investigator: Devjit Tripathy, MD
Sub-Investigator: Ralph A DeFronzo, MD

Sponsors and Collaborators

The University of Texas Health Science Center at San Antonio

Investigators

Principal Investigator:

Devjit Tripathy, MD

University of Texas

More Information

No publications provided

Responsible Party:	University oif Texas Health Science Center at San Antonio ( Devjit Tripathy/Assistant Professor, Div of Diabetes, Dept of Medicine )
Study ID Numbers:	HSC2007243H
Study First Received:	February 17, 2009
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00845182 History of Changes
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:

Metabolic Diseases
Pioglitazone
Exenatide
Glucose Intolerance
Physiological Effects of Drugs
Diabetes Mellitus
Endocrine System Diseases

Pharmacologic Actions
Body Weight
Signs and Symptoms
Hyperglycemia
Hypoglycemic Agents
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010