Effect of Pioglitazone and Exenatide on Body Weight and Beta Cell Function

NCT00845182 | Completed Phase 4 Results DMC

• 1 other identifier: HSC2007243H
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes; Healthy; Impaired Glucose Tolerance

Keywords

Type 2 diabetes pathogenesis, thiazolidinediones; impaired glucose tolerance; Incretins; Insulin secretion

Outcome Measures

Primary Outcomes (2)

• Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight

  Effect of Pioglitazone, Exenatide and combined Pioglitazone and Exenatide on body weight and beta cell function

  baseline and 6 months

• HbA1c

  change in HbA1c was measured before and after treatment in three groups

  baseline and 6 months

Secondary Outcomes (1)

• Effect Pioglitazone, Exenatide, and Pioglitazone Plus Exenatide • Insulin Sensitivity • Inflammatory Cytokines • Glucagon and Free Fatty Acids • Plasma Lipids

  6 months

Study Arms (3)

Pioglitazone

ACTIVE COMPARATOR

Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm

Drug: Pioglitazone

Exenatide

EXPERIMENTAL

Exenatide: 15 subjects will be randomized to receive Exenatide

Drug: Exenatide

Drug Pioglitazone and Drug Exentatide

EXPERIMENTAL

Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide

Drug: Pioglitazone and Exenatide

Interventions

Pioglitazone DRUG

Pioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months

Also known as: ACTOS

Pioglitazone

Exenatide DRUG

Exenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months

Also known as: BYETTA

Exenatide

Pioglitazone and Exenatide DRUG

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

Also known as: ACTOS, BYETTA

Drug Pioglitazone and Drug Exentatide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Barter Research Center, ALM VA Hospital

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Guardado-Mendoza R, Chavez AO, Jimenez-Ceja LM, Hansis-Diarte A, DeFronzo RA, Folli F, Tripathy D. Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus. Acta Diabetol. 2017 Jan;54(1):53-61. doi: 10.1007/s00592-016-0904-7. Epub 2016 Sep 13.

  PMID: 27624579 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance

Interventions

Pioglitazone; Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Devjit Tripathy
• Organization: UTexas_SanAntonio

tripathy@uthscsa.edu

2105676691

Study Officials

• Devjit Tripathy, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Study Start: June 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: January 18, 2018
• Results First Posted: March 17, 2015

Record last verified: 2017-05

Locations

US (1)