Glucagon-like Peptide 1: Evolution of an Incretin into a Treatment for Diabetes

D’Alessio DA, Vahl TP. Am J Physiol Endocrinol Metab. 2004;286:E882-E890.

Glucagon-like peptide 1 (GLP-1) is an incretin hormone secreted by the intestinal L-cells that regulates insulin secretion and glucose homeostasis. There are two types of incretins: GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Although GIP has not been found to be insulinotropic in people with diabetes, GLP-1 is insulinotropic, and there is great interest in GLP-1 and its potential use in the management of diabetes. In this review, the broad role of GLP-1 as a mediator of postprandial glucose homeostasis is described. In addition to regulating insulin secretion, GLP-1 regulates gastric emptying, suppresses glucagon secretion, reduces food intake, may regulate beta-cell mass, improves insulin sensitivity, and enhances glucose disposal. The physiological processes behind these actions is described in detail.

There is great interest in the potential use of incretins in the treatment of type 2 diabetes. Because native GLP-1 has a very short half-life, two types of compounds are currently being developed: GLP-1 analogs with extended biological half-lives and dipeptidyl peptidase IV (DPP-IV) inhibitors. Exendin-4 and NN2211, two GLP-1 receptor agonists, have shown promising results in patients with type 2 diabetes in clinical trials. DPP-IV is a protease that inactivates GLP-1, and several DPP-IV inhibitors that have the potential to increase circulating levels of GLP-1 are being studied in clinical trials. Although these results are preliminary, they have been encouraging.