Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study

Lancet. 2008 Oct 4;372(9645):1240-50. doi: 10.1016/S0140-6736(08)61206-4. Epub 2008 Sep 7.

Abstract

Background: Exenatide is an incretin mimetic that shares glucoregulatory properties with glucagon-like peptide 1 (GLP-1), and improves glycaemic control, with progressive bodyweight reductions, when administered twice a day in patients with type 2 diabetes. We compared the efficacy of a once-weekly formulation of exenatide to that of a twice daily dose.

Methods: A 30-week, randomised, non-inferiority study compared a long-acting release formulation of exenatide 2 mg administered once weekly to 10 mug exenatide administered twice a day, in 295 patients with type 2 diabetes (haemoglobin A(1c) [HbA(1c)] 8.3% [SD 1.0], mean fasting plasma glucose 9 [SD 2] mmol/L, weight 102 [SD 20] kg, diabetes duration 6.7 [SD 5.0] years). The patients were naive to drug therapy, or on one or more oral antidiabetic agents. The primary endpoint was the change in HbA(1c) at 30 weeks. This study is registered with ClinicalTrials.gov, number NCT00308139.

Findings: At 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA(1c) than those given exenatide twice a day (-1.9 [SE 0.1%] vs -1.5 [0.1%], 95% CI -0.54% to -0.12%; p=0.0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA(1c) levels of 7.0% or less (77%vs 61% of evaluable patients, p=0.0039).

Interpretation: Exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight.

Publication types

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

MeSH terms

  • Area Under Curve
  • Blood Glucose / drug effects
  • Delayed-Action Preparations
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Exenatide
  • Female
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Treatment Outcome
  • Venoms / administration & dosage
  • Venoms / adverse effects
  • Venoms / therapeutic use*

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT00308139