Addition of incretin therapy to metformin in type 2 diabetes.

Incretin-based therapies offer a new approach for the management of type 2 diabetes, with a mechanism of action distinct from any existing class of glucose-lowering agents. These drugs improve the body's ability to control blood glucose by increasing active concentrations of glucagon-like peptide-1 (GLP-1). Two approaches have been used to enhance the action of GLP-1. First, incretin mimetics (exenatide) or analogues (liraglutide) act as agonists at the GLP-1 receptor to mimic the effect of endogenous GLP-1, but are resistant to degradation by dipeptidyl peptidase-4 (DPP-4). Second, drugs that specifically inhibit DPP-4 (sitagliptin, vildagliptin, saxagliptin) are used to increase the half-life of endogenous GLP-1 that is secreted in response to food intake. Both approaches have proven efficacy for reducing the concentration of glycosylated haemoglobin (HbA1c), without inducing severe hypoglycaemic episodes or promoting weight gain. The drugs can be used alone or in combination with other oral glucose-lowering agents, such as metformin, sulphonylureas, andthiazolidinediones.