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.

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.

• Authors: M A Nauck, S Duran, D Kim, D Johns, J Northrup, A Festa, R Brodows, M Trautmann
• Journal: Diabetologia (Diabetologia) Vol. 50 Issue 2 Pg. 259-67 (Feb 2007) ISSN: 0012-186X [Print] Germany
• PMID: 17160407 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

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

Topics

• Blood Glucose (drug effects, metabolism)
• Blood Pressure
• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Therapy, Combination
• Exenatide
• Female
• Glycated Hemoglobin (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)