A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin

Diabetes Obes Metab. 2010 Dec;12(12):1058-65. doi: 10.1111/j.1463-1326.2010.01251.x.

Abstract

Aim: To test the hypothesis that glycaemic control with exenatide added to thiazolidinediones (TZDs) with or without metformin was superior to placebo.

Methods: A 26-week, multi-country (Canada, Mexico, Romania, South Africa and the USA), randomized, double-blind, placebo-controlled study compared exenatide twice-daily vs. placebo in 165 subjects suboptimally controlled with TZDs with or without metformin [HbA(1c) 8.2% (s.d. 0.9), fasting serum glucose 9.1 (2.6) mmol/l, body weight 93.9 (17.8) kg, diabetes duration 6.4 (4.3) years]. After a 2-week, single-blind, lead-in period, subjects were randomly assigned (2 : 1) to add exenatide or placebo to current regimens. The primary endpoint was HbA(1c) change at endpoint (Week 26 or last-observation-carried-forward).

Results: Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA(1c) significantly more than placebo [-0.84% (s.e. 0.20) vs. -0.10% (0.23), treatment difference -0.74% (0.16), p < 0.001)]. Mean reductions in body weight were similar in both treatments at endpoint [exenatide, -1.4 (s.e. 0.6) kg vs. placebo, -0.8 (0.7) kg, p = 0.176)]. Nearly 71% of subjects had both a reduction in HbA(1c) and body weight with exenatide compared with 54% with placebo. The most common adverse events (exenatide vs. placebo) were nausea (12% vs. 2%, p = 0.037), vomiting (8% vs. 0%, p = 0.031) and headache (4% vs. 4%). Confirmed (blood glucose <3.0 mmol/l) minor hypoglycaemia was experienced by 4 and 2% of subjects treated with exenatide and placebo, respectively. Incidence of hypoglycaemia was not significantly different between groups.

Conclusions: Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA(1c) without associated hypoglycaemia.

Publication types

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

MeSH terms

  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Exenatide
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / drug effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Nausea / chemically induced
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Placebos / administration & dosage*
  • Thiazolidinediones / administration & dosage*
  • Thiazolidinediones / adverse effects
  • Treatment Outcome
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Vomiting / chemically induced

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Placebos
  • Thiazolidinediones
  • Venoms
  • Metformin
  • Exenatide