Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Patients With Type 2 Diabetes Treated With Metformin and a Sulfonylurea

OBJECTIVE:--This study evaluated the effects of exenatide, a novel incretin mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN AND METHODS--A 30-week, double-blind, placebo-controlled study was performed in 733 subjects (aged 55 ± 10 years, BMI 33.6 ± 5.7 kg/m², A1C 8.5 ± 1.0%; means ± SD) randomized to 5 [micro]g subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 [micro]g b.i.d. and arm B escalated to 10 [micro]g b.i.d. Subjects continued taking their dose of metformin and were randomized to either maximally effective (MAX) or minimum recommended (MIN) doses of sulfonylurea. RESULTS:--Week 30 A1C changes from baseline (±SE) were -0.8 ± 0.1% (10 [micro]g), -0.6 ± 0.1% (5 [micro]g), and +0.2 ± 0.1% (placebo; adjusted P < 0.0001 vs. placebo), yielding placebo-adjusted reductions of -1.0% (10 [micro]g) and -0.8% (5 [micro]g). In the evaluable population, exenatide-treated subjects were more likely to achieve A1C