Effects of Exenatide Combined with Lifestyle Modification in Patients with Type 2 Diabetes

OBJECTIVE: To determine the effect of a lifestyle modification program plus exenatide versus lifestyle modification program plus placebo on weight loss in overweight or obese participants with type 2 diabetes treated with metfonnin and/or sulfonylurea. METHODS: In this 24-week, multicenter, randomized, double-blind, placebo-controlled study, 194 patients participated in a lifestyle modification program, consisting of goals of 600 kcal/day deficit and physical activity of at least 2.5 hours/week. Participants were randomized to 5 mu g exenatide twice daily injection + lifestyle modification program (n = 96) or placebo + lifestyle modification program (n = 98), and after 4 weeks increased their exenatide dose to 10 mu g twice daily or volume equivalent of placebo. RESULTS: Baseline characteristics: (mean standard deviation) age, 54.8 +/- 9.5 years; weight, 95.5 +/- 16.0 kg; hemoglobin A(1c), 7.6 +/- 0.8%. At 24 weeks (least squares mean standard error), treatments showed similar decreases in caloric intake (-378 +/- 58 vs 295 58 kcal/day, exenatide + lifestyle modification program vs placebo + lifestyle modification program, P = .27) and increases in exercise-derived energy expenditure. Exenatide + lifestyle modification program showed greater change in weight (-6.16 +/- 0.54 kg vs -3.97 +/- 0.52 kg, P = .003), hemoglobin A(1c) (-1.21 +/- 0.09% vs -0.73 +/- 0.09%, P < .0001), systolic (-9.44 +/- 1.40 vs -1.97 +/- 1.40 mm Hg, P < .001) and diastolic blood pressure (-2.22 +/- 1.00 vs 0.47 +/- 0.99 mm Hg, P = .04). Nausea was reported more for exenatide + lifestyle modification program than placebo + lifestyle modification program (44.8% vs 19.4%, respectively, P < .001), with no difference in withdrawal rates due to adverse events (4.2% vs 5.1%, respectively, P = 1.0) or rates of hypoglycemia. CONCLUSIONS: When combined with lifestyle modification, exenatide treatment led to significant weight loss, improved glycemic control, and decreased blood pressure compared with lifestyle modification alone in overweight or obese participants with type 2 diabetes on metformin and/or sulfonylurea treatment. (c) 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, 468.e9-468.e17