The American Journal of Medicine
Volume 123, Issue 3, Supplement , Pages S28-S37, March 2010

Incretin-Based Therapies: Review of Current Clinical Trial Data

  • Anne Peters, MD, CDE

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Anne Peters, MD, CDE, 150 North Robertson Boulevard, Suite 210, Beverly Hills, California 90211

Clinical Diabetes Programs, University of Southern California, Los Angeles, California, USA

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.

Keywords: Exenatide, GIP, GLP-1, Incretin, Sitagliptin, Type 2 diabetes mellitus

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  • ⁎ After submission of manuscripts, liraglutide received US FDA approval on January 25, 2010.

 Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

PII: S0002-9343(09)01078-X

doi:10.1016/j.amjmed.2009.12.007

The American Journal of Medicine
Volume 123, Issue 3, Supplement , Pages S28-S37, March 2010

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