Vol 8, No 11 (2007): Practical Diabetology
Other materials agreed with the Editors
Published online: 2008-02-04
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 Praktyczna 2007;8(11):431-443.
Abstract
AIMS/HYPOTHESIS. The aim of this 52-week, openlabel,
noninferiority 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 μg twice daily for 4 weeks, 10 μg 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 exenatide was non-inferior to that achieved with biphasic insulin aspart [mean ± SEM, HbA1c 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 [betweengroup difference -5.4 kg (95% CI -5.9 to -5.0)]. 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 HbA1c 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.
MATERIALS AND METHODS. Patients on metformin and a sulfonylurea were randomised to exenatide (n = 253; 5 μg twice daily for 4 weeks, 10 μg 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 exenatide was non-inferior to that achieved with biphasic insulin aspart [mean ± SEM, HbA1c 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 [betweengroup difference -5.4 kg (95% CI -5.9 to -5.0)]. 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 HbA1c 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.
Keywords: biphasic insulin aspartexenatideincretin mimeticnon-inferioritytype 2 diabetesweight reduction