Exenatide: its position in the treatment of type 2 diabetes

Type 2 diabetic patients who have not achieved adequate glucose control at the maximum tolerated doses of their oral therapies currently have no alternative other than insulin. A new approach has been developed, using the glucoregulatory properties of the intestinal incretin hormone glucagon-like peptide-1 (GLP-1). This has resulted in the development of a new therapeutic class, the incretin mimetics, of which exenatide is the first to have been approved. Exenatide can bind to the endogenous receptors of GLP-1 and mimic its glucoregulatory actions. It improves glycemic control by acting on the key organs involved in glucose homeostasis: it stimulates insulin secretion and suppresses glucagon secretion in a glucose-dependent way, slows gastric emptying and reduces food intake. It consequently produces significant reductions in fasting and postprandial hyperglycemia. Various clinical studies, both versus placebo and versus insulin, have shown a significant decrease in HbA1c levels (of about 1%), accompanied by weight loss, in patients treated with exenatide. Exenatide efficacy is sustained and all the studies have shown a comparable tolerance profile. The most frequently reported adverse effects were nausea and hypoglycemia when the patient received concomitant sulfonylurea therapy. The aim of this article is to summarize main clinical data on exenatide and to discuss its position in current therapeutic strategy.