Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4).

Thornberry, Nancy A; Gallwitz, Baptist
Best practice & research. Clinical endocrinology & metabolism; 2009 Aug;23(4):479-86. PMID: 19748065
Department of Metabolic Disorders, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.


Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of the incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The first available DPP-4 inhibitors are sitagliptin and vildagliptin. These compounds are orally active and have been shown to be efficacious and well tolerated. Two additional DPP-4 inhibitors are under review, and there are several others in clinical development. This article gives an overview on the mechanism of action of DPP-4 inhibitors and focuses on their development and their important physiological actions with regard to the treatment of type 2 diabetes.