Incretin-based therapies: review of current clinical trial data

Am J Med. 2010 Mar;123(3 Suppl):S28-37. doi: 10.1016/j.amjmed.2009.12.007.

Abstract

Incretin hormones are secreted in response to food ingestion and help manage glycemic control by regulating insulin and glucagon release, slowing gastric emptying, and reducing caloric intake. Glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, secreted from the L-cells of the lower gut and K-cells of the intestines, respectively, are responsible for these incretin effects, which are reduced in patients with type 2 diabetes mellitus. Initially, the rapid degradation of either incretin by dipeptidyl peptidase-4 (DPP-4) complicated the development of viable therapeutics based on either hormone. However, the US Food and Drug Administration (FDA) has approved 2 incretin-based therapies in which their mechanisms of action augment or amplify the effects of naturally occurring GLP-1. Exenatide, a first-in-class GLP-1 receptor agonist, exhibits the same mechanisms of action as native GLP-1. Sitagliptin inhibits the DPP-4 enzyme, thus increasing the half-life of endogenous GLP-1. This review examines data from recent GLP-1 receptor agonist and DPP-4 inhibitor studies in patients with type 2 diabetes, as well as data on other incretin-based therapies in clinical development.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptidyl-Peptidase IV Inhibitors
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / agonists
  • Incretins / antagonists & inhibitors
  • Incretins / physiology*
  • Peptides / therapeutic use
  • Pyrazines / therapeutic use
  • Receptors, Glucagon / agonists
  • Sitagliptin Phosphate
  • Triazoles / therapeutic use
  • Venoms / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins
  • Peptides
  • Pyrazines
  • Receptors, Glucagon
  • Triazoles
  • Venoms
  • Exenatide
  • Sitagliptin Phosphate