DPP-4 inhibitors as a new target of action for Type 2 diabetes mellitus: a focus on vildagliptin

Abstract

The purpose of this review is to highlight the role of the incretin system and discuss the role of dipeptidyl peptidase (DPP)-4 inhibitors as potential treatment for diabetes, drawing attention to some of the available clinical trial data that support the use of such agents. The DPP-4 enzyme is involved in the breakdown of glucagon-like peptide (GLP)-1, an incretin that has a very short half-life. DPP-4 inhibitors delay the degradation of GLP-1, in turn extending the action of insulin and suppressing the release of glucagon. Endogenous and exogenous GLP-1 not only stimulates the release of insulin, but also reduces the secretion of glucagon. The latter action may be very important and represents a neglected aspect of the treatment of diabetes. The focus of the review is on one of the DPP-4 inhibitors, vildagliptin, since there is much recently published data on this drug. Vildagliptin has been shown to decrease hemoglobin A_1C by 0.5–0.8% either alone or in combination. Generally, it is found to be well tolerated and safe, at least in the short term.

Keywords::

• diabetes
• dipeptidyl peptidase-4
• glucagon
• glucagon-like peptide-1
• incretin
• insulin

Financial disclosure

Diabetes research at Tulane University Health Sciences Center is supported in part by Susan Harling Robinson Fellowship in Diabetes Research and the Tullis-Tulane Alumni Chair in Diabetes.

Duality of Interest for Dr Vivian Fonseca: Research Support (to Tulane): Grants from GlaxoSmithKline, Novartis, Takeda, AstraZeneca, Pfizer, Sanofi-Aventis, Eli Lilly, NIH and ADA. Honoraria for Consulting and Lectures (to Tulane): GlaxoSmithKline, Novartis, Takeda, Pfizer, Sanofi-Aventis and Eli Lilly.