The role of incretin-based therapy in type 2 diabetes

One of the major incretins in humans, glucagon-like peptide 1 (GLP-1), is a glucose-lowering, intestinal-derived hormone secreted from distal ileum and part of the colon. Food intake stimulates GLP-1 secretion, which in turn increases insulin secretion from pancreatic β cells, and suppresses glucagon secretion from pancreatic α cells. Because GLP-1 stimulates insulin secretion and inhibits glucagon secretion in a blood glucose-dependent manner, it rarely causes hypoglycemia. GLP-1 also increases central sensation of satiety and delays peripheral gastric emptying, thus has an anti-appetite and weight reduction effect. Once secreted, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to form biologically inactive metabolites. Two strategies are applied to increase incretin action in type 2 diabetic patients, administration of injectable GLP-1 mimetics that are DPP-4 resistant and thus longer-acting, or of small molecule DPP-4 inhibitors to inhibit DPP-4 degradation of endogenous GLP-1 via oral route. In this review, incretin biology and the potential clinical use of incretin-based therapy in type 2 diabetes mellitus will be discussed.