Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial

Ann Intern Med. 2011 Jan 18;154(2):103-12. doi: 10.7326/0003-4819-154-2-201101180-00300. Epub 2010 Dec 6.

Abstract

Background: Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A₁(c) (HbA₁(c)) targets.

Objective: To test whether twice-daily exenatide injections reduce HbA₁(c) levels more than placebo in people receiving insulin glargine.

Design: Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA₁(c) level at site, performed from October 2008 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. (ClinicalTrials.gov registration number: NCT00765817)

Setting: 59 centers in 5 countries.

Patients: Adults with type 2 diabetes and an HbA₁(c) level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents).

Intervention: Assignment by a centralized, computer-generated, random-sequence interactive voice-response system to exenatide, 10 µg twice daily, or placebo for 30 weeks.

Measurements: The primary outcome was change in HbA₁(c) level. Secondary outcomes included the percentage of participants with HbA₁(c) values of 7.0% or less and 6.5% or less, 7-point self-monitored glucose profiles, body weight, waist circumference, insulin dose, hypoglycemia, and adverse events.

Results: 112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study. The HbA₁(c) level decreased by 1.74% with exenatide and 1.04% with placebo (between-group difference, -0.69% [95% CI, -0.93% to -0.46%]; P < 0.001). Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo (between-group difference, -2.7 kg [CI, -3.7 to -1.7]). Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d. The estimated rate of minor hypoglycemia was similar between groups. Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events (P < 0.010); rates of nausea (41% vs. 8%), diarrhea (18% vs. 8%), vomiting (18% vs. 4%), headache (14% vs. 4%), and constipation (10% vs. 2%) were higher with exenatide than with placebo.

Limitations: The study was of short duration. There were slight imbalances between groups at baseline in terms of sex, use of concomitant glucose-lowering medications, and HbA₁(c) levels, and more exenatide recipients than placebo recipients withdrew because of adverse events.

Conclusion: Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment. Adverse events of exenatide included nausea, diarrhea, vomiting, headache, and constipation.

Primary funding source: Alliance of Eli Lilly and Company and Amylin Pharmaceuticals.

Publication types

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

MeSH terms

  • Aged
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Exenatide
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Injections, Subcutaneous
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use
  • Insulin Glargine
  • Insulin, Long-Acting
  • Male
  • Metformin / administration & dosage
  • Metformin / therapeutic use
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Peptides / therapeutic use
  • Pioglitazone
  • Sensitivity and Specificity
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / therapeutic use
  • Venoms / administration & dosage*
  • Venoms / adverse effects
  • Venoms / therapeutic use

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Peptides
  • Thiazolidinediones
  • Venoms
  • Insulin Glargine
  • Metformin
  • Exenatide
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT00765817