Update on incretin hormones.

Abstract

The incretin hormones glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the intestine following oral ingestion of nutrients. Incretins promote insulin secretion, while GLP-1 also inhibits glucagon release and gastric emptying, minimizing postprandial glucose excursions. The incretins share similar effects on the pancreatic β cell; however, there are a number of differences in extrapancreatic actions. Type 2 diabetes (T2DM) is associated with abnormal incretin physiology, and although treatment with GIP is ineffective, GLP-1 effects are preserved. The current incretin-based approaches to T2DM include the GLP-1 agonists that are resistant to the serine protease dipeptidylpeptidase-4 (DPP4), which normally rapidly degrades the incretins, and DPP4 inhibitors (DPP4i). Incretin-based treatments have provoked much interest due to use-associated weight loss (GLP-1 agonists), minimal hypoglycemia, and potential for positive effects on pancreatic β cell biology and the cardiovascular system. However, the long-term safety of these agents has yet to be established. This review outlines the current understanding of incretin biology, available data pertaining to incretin-based treatment in T2DM, and differences between GLP-1 and DPP4i therapy. © 2012 New York Academy of Sciences.