Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial Journal Article uri icon
  • BACKGROUND: Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A(1)(c) (HbA(1)(c)) targets. OBJECTIVE: To test whether twice-daily exenatide injections reduce HbA(1)(c) levels more than placebo in people receiving insulin glargine. DESIGN: Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA(1)(c) level at site, performed from October 2008 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. ( registration number: NCT00765817) SETTING: 59 centers in 5 countries. PATIENTS: Adults with type 2 diabetes and an HbA(1)(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 microg twice daily, or placebo for 30 weeks. MEASUREMENTS: The primary outcome was change in HbA(1)(c) level. Secondary outcomes included the percentage of participants with HbA(1)(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 HbA(1)(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 HbA(1)(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.

  • Link to Article
    publication date
  • 2011
  • published in
  • Adverse Effects
  • Clinical Trials
  • Diabetes
  • Drugs and Drug Therapy
  • Randomized Controlled Trials
  • Additional Document Info
  • 154
  • issue
  • 2