Expanded Use of Exenatide in the Management of Type 2 Diabetes

Exenatide is an incretin mimetic agent that possesses multiple mechanisms of glucose lowering. It enhances glucose-dependent insulin secretion by the pancreatic β-cell, leading to insulin release in the presence of elevated glucose concentrations. It also moderates glucagon secretion and lowers serum glucagon concentrations during periods of hyperglycemia. Lower glucagon concentrations lead to decreased hepatic glucose output and decreased insulin demand. Exenatide also slows gastric emptying, thereby reducing the rate at which meal-derived glucose appears in the circulation, thereby further decreasing postprandial blood glucose levels. Finally, administration of exenatide has been shown to reduce subsequent food intake by increasing satiety, often resulting in weight loss.1Exenatide is indicated as an adjunctive therapy to improve glycemic control in patients with type 2 diabetes who are taking metformin and/or a sulfonylurea but have not achieved adequate glycemic control.1 To decrease gastrointestinal intolerance, exenatide is initiated at 5 μg subcutaneously twice daily and increased after 1 month to a target maintenance dose of 10 μg twice daily. Three 30-week studies as add-on therapy to sulfonylurea, metformin, and sufonylurea/metformin have demonstrated hemoglobin A1c (A1C) reductions of ∼ 1% with an average weight loss of 1.4–1.8 kg.2–4 Therapy was generally well tolerated with the most frequent adverse events classified as mild or moderate and gastrointestinal in nature. Severe hypoglycemia was not observed during these studies.2–4The concurrent use of exenatide with insulin, meglitinides, or α-glucosidase inhibitors has not been reported. Published information regarding the use of exenatide with thiazolidinediones (TZDs) is limited to two abstracts.5,6 The objective of this study was to determine the effectiveness and safety of off-label exenatide use in patients with type 2 diabetes.A retrospective review of the electronic medical records of one private-practice endocrinologist was conducted. The study was …