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

  1. David M. Kendall, MD1,
  2. Matthew C. Riddle, MD2,
  3. Julio Rosenstock, MD3,
  4. Dongliang Zhuang, PHD4,
  5. Dennis D. Kim, MD4,
  6. Mark S. Fineman, BS4 and
  7. Alain D. Baron, MD4
  1. 1International Diabetes Center and University of Minnesota, Minneapolis, Minnesota
  2. 2Section of Diabetes, Oregon Health & Science University, Portland, Oregon
  3. 3Dallas Diabetes and Endocrine Center, Dallas, Texas
  4. 4Amylin Pharmaceuticals, San Diego, California
  1. 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

Abstract

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.

Footnotes

  • D.M.K. has served on an advisory panel for Amylin/Lilly; has received honoraria from Eli Lilly, Amylin, Novo Nordisk, and Merck; and has received research/grant support from Eli Lilly, Amylin, Novo Nordisk, Merck, and GlaxoSmithKline. M.C.R. has received honoraria/consulting fees from Amylin and Amylin/Lilly. J.R. has served on advisory boards for and has received honoraria/consulting fees from Pfizer, Sanofi-Aventis, Novo Nordisk, GlaxoSmithKline, Takeda, Centocor, Johnson & Johnson, and Amylin and has received grant support from Merck, Pfizer, Sanofi-Aventis, Novo Nordisk, Eli Lilly, GlaxoSmithKline, Takeda, Novartis, AstraZeneca, Amylin, Sankyo, and MannKind.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted January 31, 2005.
    • Received September 27, 2004.
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