Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes

Abstract

OBJECTIVE - In patients with type 2 diabetes, exenatide reduces A1C, postprandial and fasting glucose, and weight. In this study we investigated the effects of continuous exenatide administration from a long-acting release (LAR) formulation. RESEARCH DESIGN AND METHODS - In this randomized, placebo-controlled phase 2 study, exenatide LAR (0.8 or 2.0 mg) was administered subcutaneously once weekly for 15 weeks to subjects with type 2 diabetes (n = 45) suboptimally controlled with metformin (60%) and/or diet and exercise (40%): 40% female, A1C (mean ± SD) 8.5 ± 1.2%, fasting plasma glucose 9.9 ± 2.3 mmol/l, weight 106 ± 20 kg, and diabetes duration 5 ± 4 years. RESULTS - From baseline to week 15, exenatide LAR reduced mean ± SE A1C by -1.4 ± 0.3% (0.8 mg) and -1.7 ± 0.3% (2.0 mg), compared with +0.4 ± 0.3% with placebo LAR (P < 0.0001 for both). A1C of ≤7% was achieved by 36 and 86% of subjects receiving 0.8 and 2.0 mg exenatide LAR, respectively, compared with 0% of subjects receiving placebo LAR. Fasting plasma glucose was reduced by -2.4 ± 0.9 mmol/l (0.8 mg) and -2.2 ± 0.5 mmol/l (2.0 mg) compared with +1.0 ± 0.7 mmol/l with placebo LAR (P ≤ 0.001 for both). Exenatide LAR reduced self-monitored postprandial hyperglycemia. Subjects receiving 2.0 mg exenatide LAR had body weight reductions (-3.8 ± 1.4 kg) (P ≤ 0.05), whereas body weight was unchanged with both placebo LAR and the 0.8-mg dose. Mild nausea was the most frequent adverse event. No subjects treated with exenatide LAR withdrew from the study. CONCLUSIONS - Exenatide LAR offers the potential of 24-h glycemic control and weight reduction with a novel once-weekly treatment for type 2 diabetes. © 2007 by the American Diabetes Association.