The incretin effect and its potentiation by glucagon-like peptide 1-based therapies: a revolution in diabetes management.
The incretin effect is a phenomenon in which enteral glucose administration provokes greater insulin secretion than intravenous administration. The main incretins, glucose-dependent insulinotropic peptide and glucagon-like peptide (GLP)-1 are defective in Type 2 diabetes; whereas glucose-dependent insulinotropic peptide displays diminished effectiveness, GLP-1 secretion is decreased; thus, GLP-1 was a stronger candidate for a new class of anti-diabetic agents designed to potentiate the incretin effect. In the past decade, GLP-1 mimetics, peptidase inhibitors and GLP-1 have been developed. Early randomised trials show that these agents contribute to glucose homeostasis and enhance beta-cell function, without causing hypoglycaemia or weight gain. This review includes an historical perspective, physiology of incretins, and discussions of the pathophysiology in Type 2 diabetes, pharmacology of the main agents and randomised clinical trials published to date.
Roges
Octaviano A
OA
The Whittier Institute for Diabetes, 9894 Genesee Avenue, La Jolla, CA 92037, USA. roges.octaviano@scrippshealth.org
Baron
Marilyn
M
Philis-Tsimikas
Athena
A
D000818:Animals; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data / Q000639:trends; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D019468:Disease Management; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism / Q000627:therapeutic use
D010446:Peptide Fragments; D052216:Glucagon-Like Peptide 1