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Diabetes Care 28:1083-1091, 2005
© 2005 by the American Diabetes Association, Inc.

Emerging Treatments and Technologies
Original Article

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

David M. Kendall, MD1, Matthew C. Riddle, MD2, Julio Rosenstock, MD3, Dongliang Zhuang, PHD4, Dennis D. Kim, MD4, Mark S. Fineman, BS4 and Alain D. Baron, MD4

1 International Diabetes Center and University of Minnesota, Minneapolis, Minnesota
2 Section of Diabetes, Oregon Health & Science University, Portland, Oregon
3 Dallas Diabetes and Endocrine Center, Dallas, Texas
4 Amylin Pharmaceuticals, San Diego, California

Address correspondence and reprint requests to Alain D. Baron, MD, Senior Vice President, Research, Amylin Pharmaceuticals, 9360 Towne Centre Dr., Suite 110, San Diego, CA 92121. E-mail: abaron{at}amylin.com

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 µg subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 µg b.i.d. and arm B escalated to 10 µg 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 µg), –0.6 ± 0.1% (5 µg), and +0.2 ± 0.1% (placebo; adjusted P < 0.0001 vs. placebo), yielding placebo-adjusted reductions of –1.0% (10 µg) and –0.8% (5 µg). In the evaluable population, exenatide-treated subjects were more likely to achieve A1C ≤7% than placebo-treated subjects (34% [10 µg], 27% [5 µg], and 9% [placebo]; P < 0.0001). Both exenatide arms demonstrated significant weight loss (–1.6 ± 0.2 kg from baseline each exenatide arm, –0.9 ± 0.2 kg placebo; P ≤ 0.01 vs. placebo). Mild or moderate nausea was the most frequent adverse event. The incidence of mild/moderate hypoglycemia was 28% (10 µg), 19% (5 µg), and 13% (placebo) and appeared lower with MIN than with MAX sulfonylurea treatment.

CONCLUSIONS—Exenatide significantly reduced A1C in patients with type 2 diabetes unable to achieve adequate glycemic control with maximally effective doses of combined metformin-sulfonylurea therapy. This improvement in glycemic control was associated with no weight gain and was generally well tolerated.

Abbreviations: AUC, area under the curve • GLP-1, glucagon-like peptide 1 • ITT, intent to treat


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Find additional patient-related information at:

Exenatide: A New Type of Drug to Treat Type 2 Diabetes


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