Glucagon-like peptide-1-based therapies: new developments and emerging data

Type 2 diabetes is a chronic, progressive disease characterized by an inexorable decline in beta-cell function. Current treatments fail to manage this continued beta-cell failure, and eventually patients with type 2 diabetes will require insulin therapy. The 'ideal' therapy for type 2 diabetes needs to provide not only effective glycaemic control with no weight gain and preferably, no hypoglycaemia, but also address continued beta-cell deterioration. The development of glucagon-like peptide-1 (GLP-1) based therapies provides an alternative to traditional oral antidiabetic drugs. Here, we present the evidence base showing that the incretin mimetics (exenatide, exenatide long-acting release and liraglutide) and the incretin enhancers (sitagliptin and vildagliptin) offer significant glycaemic improvements over existing treatments, with low rates of hypoglycaemia. In addition, we present evidence to show that incretin mimetics are associated with significant weight loss, in contrast to incretin enhancers, which are weight neutral. Finally, we summarize and discuss the key features of the incretin enhancers and incretin mimetics in terms of glycaemic control, side effects and flexibility of treatment regimen.