The Incretin Mimetic Exenatide as a Monotherapy in Patients with Type 2 Diabetes

Abstract

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 μg twice-daily, 10 μg once-daily, or 20 μg 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 μg twice-daily for 4 weeks followed by 10 μg for 26 weeks. Subjects treated with metformin continued oral therapy.

Results:

Monotherapeutic treatment with 10 μg of exenatide twice-daily for 28 days resulted in significant mean reductions in glycosylated hemoglobin (A1C) 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 A1C 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-to-moderate hypoglycemia was low, with no severe hypoglycemia.

Conclusions:

Exenatide twice-daily monotherapy resulted in glycemic improvements and reductions in body weight comparable to that of exenatide combination therapy with metformin in patients with type 2 diabetes.