The incretin mimetic exenatide as a monotherapy in patients with type 2 diabetes

Background: Exenatide is an adjunctive therapy for type 2 diabetes, and preliminary evidence suggests that its glucoregulatory effects may be similar in the absence of oral therapy. Methods: Study A was a randomized, double-blind, placebo-controlled study of 99 patients with type 2 diabetes that received either 10 mu g twice-daily, 10 mu g once-daily, or 20 mu g once-daily exenatide or placebo for 28 days in the absence of background pharmacotherapy. Study B was an open-label extension of a short-term study of 127 patients with type 2 diabetes treated with metformin or diet and exercise. Patients received exenatide 5 mu g twice-daily for 4 weeks followed by 10 mu g for 26 weeks. Subjects treated with metformin continued oral therapy. Results: Monotherapeutic treatment with 10 mu g of exenatide twice-daily for 28 days resulted in significant mean reductions in glycosylated hemoglobin (AIC) of -0.4 +/- 0.1% and fasting plasma glucose of -36.1 +/- 11.0 mg/dL compared to increases of +0.2 +/- 0.1% and +11.0 +/- 12.7 mg/dL with placebo. Self-monitored blood glucose profiles showed significant mean reductions in daily blood glucose concentrations in exenatide-treated patients compared to placebo. Exenatide treatment for 30 weeks in an open-label extension study resulted in similar mean reductions from baseline in AIC and body weight in patients treated with diet and exercise alone (-1.0 +/- 0.2% and -4.3 +/- 1.3 kg, respectively) as those treated on a background of metformin (-0.9 +/- 0.1% and -3.7 +/- 0.5 kg, respectively). In both studies, the most frequent adverse events were gastrointestinal and predominantly mild to moderate in intensity. Incidence of mild-tomoderate hypoglycemia was low, with no severe hypoglycernia. Conclusions: Exenatide twice-daily monotherapy resulted in glycemic improvements and reductions in body weight comparable to that of exenatide combination therapy with metformin