Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes

This randomized, double-blind, placebo-controlled clinical trial was one of the pivotal studies that supported the approval of exenatide as the first incretin mimetic for the treatment of type 2 diabetes. The study enrolled 377 patients with type 2 diabetes inadequately controlled on maximally tolerated sulfonylurea doses, randomized to exenatide 5 µg, 10 µg (twice daily), or placebo for 30 weeks.

Results demonstrated that exenatide 10 µg reduced HbA1c by -0.86% from baseline, while the placebo group showed an increase of +0.12% (p<0.002). Approximately 41% of patients in the exenatide 10 µg group achieved HbA1c ≤7%. Notably, exenatide promoted progressive weight loss of -1.6 kg in the 10 µg group, contrasting with the typical weight gain associated with conventional hypoglycemic therapies.

The most common adverse effects were gastrointestinal, particularly mild to moderate nausea, which decreased over the course of treatment. The incidence of hypoglycemia was relatively low and generally associated with concomitant sulfonylurea use.

This study was a historic milestone in diabetology for inaugurating a new therapeutic class based on the incretin effect, demonstrating that it was possible to improve glycemic control with simultaneous weight loss — a benefit previously unattainable with available therapies. The data presented here directly contributed to the FDA approval of exenatide (Byetta) in 2005.