Physiology of Incretin Hormones and the Basis for DPP-4 Inhibitors

With the rising prevalence of diabetes, new therapies that provide glucosecontrol are needed. Although many medications are available, tight glucosecontrol is still a challenge. In this article, the physiology of glucosehomeostasis is explored with respect to type 2 diabetes. The incretin effectis explained in detail, and the incretin hormones, glucose-dependentinsulinotrophic polypeptide and glucagon-like peptide 1, are investigated aswell as their contribution to type 2 diabetes therapy. Studies involvingdipeptidyl-peptidase 4 (DPP-4) inhibitors are summarized as to their effectson glucose homeostasis. Specifically, vildagliptin (Galvus®; NovartisInternational AG, Basel, Switzerland) and sitagliptin (JanuviaTM; Merck& Co, Inc, Whitehouse Station, NJ) are described. The use and efficacy ofthe currently available incretin mimetic, exenatide (Byetta®; AmylinPharmaceuticals, Inc and Eli Lilly and Company, San Diego, Calif, andIndianapolis, Ind), are briefly discussed. Throughout this article, therationale for the use of DPP-4 inhibitors is presented.