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.
RCT Entities:
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: Philip Raskin; Elsie Allen; Priscilla Hollander; Andrew Lewin; Robert A Gabbay; Peter Hu; Bruce Bode; Alan Garber Journal: Diabetes Care Date: 2005-02 Impact factor: 19.112
Authors: Ralph A DeFronzo; Robert E Ratner; Jenny Han; Dennis D Kim; Mark S Fineman; Alain D Baron Journal: Diabetes Care Date: 2005-05 Impact factor: 19.112
Authors: Mark S Fineman; Thomas A Bicsak; Larry Z Shen; Kristin Taylor; Eling Gaines; Amanda Varns; Dennis Kim; Alain D Baron Journal: Diabetes Care Date: 2003-08 Impact factor: 19.112
Authors: Juan José Marín-Peñalver; Iciar Martín-Timón; Cristina Sevillano-Collantes; Francisco Javier Del Cañizo-Gómez Journal: World J Diabetes Date: 2016-09-15