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

Abstract

OBJECTIVE - This study evaluated the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy. RESEARCH DESIGN AND METHODS - This was a triple-blind, placebo-controlled, 30-week study conducted at 101 sites in the U.S. After a 4-week, single-blind, placebo lead-in period, 377 subjects were randomized (60% men, age 55 ± 11 years, BMI 33 ± 6 kg/m2, HbA1c 8.6 ± 1.2% [±SD]) and began 4 weeks at 5 μg subcutaneous exenatide twice daily (before breakfast and dinner; arms A and B) or placebo. Subsequently, subjects in arm B were escalated to 10 μg b.i.d. exenatide. All subjects continued sulfonylurea therapy. RESULTS - At week 30, HbA1c changes from baseline were -0.86 ± 0.11, -0.46 ± 0.12, and 0.12 ± 0.09% (±SE) in the 10-μg, 5-μg, and placebo arms, respectively (adjusted P < 0.001). Of evaluable subjects with baseline HbA1c > 7% (n = 237), 41% (10 μg), 33% (5 μg), and 9% (placebo) achieved HbA1c ≤ 7% (P < 0.001). Fasting plasma glucose concentrations decreased in the 10-μg arm compared with placebo (P < 0.05). Subjects in the exenatide arms had dose-dependent progressive weight loss, with an end-of-study loss in the 10-μg exenatide arm of -1.6 ± 0.3 kg from baseline (P < 0.05 vs. placebo). The most frequent adverse events were generally mild or moderate and gastrointestinal in nature. No severe hypoglycemia was observed. CONCLUSIONS - Exenatide significantly reduced HbA1c in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide was generally well tolerated and was associated with weight loss.