The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial

Ann Intern Med. 2007 Apr 3;146(7):477-85. doi: 10.7326/0003-4819-146-7-200704030-00003.

Abstract

Background: Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported.

Objective: To compare the effects of exenatide versus placebo on glycemic control.

Design: Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005.

Setting: 49 sites in Canada, Spain, and the United States.

Patients: 233 (exenatide group, n = 121; placebo group, n = 112) patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin). Mean (+/-SE) baseline glycated hemoglobin A1c level was 7.9% +/- 0.1%.

Interventions: Subcutaneous abdominal injections of 10 microg of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks.

Measurements: The primary outcome was change from baseline in hemoglobin A1c level. Other outcomes were fasting serum glucose level, body weight, self-monitored blood glucose level, and any adverse events.

Results: Exenatide treatment reduced hemoglobin A(1c) level (mean difference, -0.98% [95% CI, -1.21% to -0.74%]), serum fasting glucose level (mean difference, -1.69 mmol/L [-30.5 mg/dL] [CI, -2.22 to -1.17 mmol/L {-40.0 to -21.1 mg/dL}]), and body weight (mean difference, -1.51 kg [CI, -2.15 to -0.88 kg]). Sixteen percent of patients in the exenatide group and 2% of patients in the placebo group discontinued treatment because of adverse events. In the exenatide group, 40% (n = 48) of patients experienced nausea (mostly mild [n = 21] or moderate [n = 19]), 13% experienced vomiting, and 11% experienced hypoglycemia. In the placebo group, 15% of patients experienced nausea, 1% experienced vomiting, and 7% experienced hypoglycemia.

Limitations: Combinations with TZDs and sulfonylureas were not tested. Trial duration was relatively short. Only 71% and 86% of patients in the exenatide and placebo groups, respectively, completed the study.

Conclusions: Exenatide therapy improved glycemic control, reduced body weight, and caused gastrointestinal symptoms more than placebo in patients with type 2 diabetes that was suboptimally controlled with TZD therapy. ClinicalTrials.gov registration number: NCT00099320. For more information on exenatide click here.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Blood Glucose Self-Monitoring
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Exenatide
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Subcutaneous
  • Insulin-Secreting Cells / physiology
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Nausea / chemically induced
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Thiazolidinediones / therapeutic use*
  • Venoms / adverse effects
  • Venoms / therapeutic use*
  • Vomiting / chemically induced
  • Weight Loss / drug effects

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Thiazolidinediones
  • Venoms
  • Metformin
  • Exenatide
  • 2,4-thiazolidinedione

Associated data

  • ClinicalTrials.gov/NCT00099320