A Comparison of Twice-Daily Exenatide and Biphasic Insulin Aspart in Patients With Type 2 Diabetes Who Were Suboptimally Controlled With Sulfonylurea and Metformin: A Non-Inferiority Study

Diabetologia. 2007 Feb;50(2):259-67. doi: 10.1007/s00125-006-0510-2. Epub 2006 Dec 8.

Abstract

Aims/hypothesis: The aim of this 52-week, open-label, non-inferiority trial was to compare the safety and efficacy of exenatide (an incretin mimetic) with that of biphasic insulin aspart.

Materials and methods: Patients on metformin and a sulfonylurea were randomised to exenatide (n = 253; 5 microg twice daily for 4 weeks, 10 microg thereafter) or biphasic insulin aspart (n = 248; twice-daily doses titrated for optimal glucose control), while continuing with metformin and sulfonylurea treatment.

Results: Glycaemic control achieved with exenatide was non-inferior to that achieved with biphasic insulin aspart (mean+/-SEM, HbA(1c) change: exenatide -1.04 +/- 0.07%, biphasic insulin aspart -0.89 +/- 0.06%; difference -0.15 [95% CI -0.32 to 0.01]%). Exenatide-treated patients lost weight, while patients treated with biphasic insulin aspart gained weight [between-group difference -5.4 (95% CI -5.9 to -5.0) kg]. Both treatments reduced fasting serum glucose (exenatide -1.8 +/- 0.2 mmol/l, p < 0.001; biphasic insulin aspart -1.7 +/- 0.2 mmol/l, p < 0.001). Greater reductions in postprandial glucose excursions following morning (p < 0.001), midday (p = 0.002) and evening meals (p < 0.001) were observed with exenatide. The withdrawal rate was 21.3% (54/253) for exenatide and 10.1% (25/248) for biphasic insulin aspart. Nausea (33% incidence, 3.5% discontinuation) was the most common adverse event observed with exenatide.

Conclusions/interpretation: Exenatide treatment resulted in HbA(1c) reduction similar to biphasic insulin aspart and provided better postprandial glycaemic control, making it a potential alternative for the treatment of type 2 diabetes. Treatment with biphasic insulin aspart was associated with weight gain and lower risk of adverse gastrointestinal events. Although the availability of glucose-lowering agents associated with weight reduction may be considered a therapeutic advance, the long-term implications of progressive weight reduction observed with exenatide have yet to be defined.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Pressure
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Exenatide
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Lipids / blood
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Peptides / therapeutic use*
  • Sulfonylurea Compounds / therapeutic use
  • Venoms / therapeutic use*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Peptides
  • Sulfonylurea Compounds
  • Venoms
  • Metformin
  • Exenatide