Dipeptidyl Peptidase-4 as a New Target of Action for Type 2 Diabetes Mellitus: A Systematic Review

Type 2 diabetes mellitus is a metabolic disease leading to microvascular and macrovascular complications including coronary artery disease and stroke. Management of diabetes has been challenging, particularly in the presence of the enormous prevalence of obesity. In recent years, various inhibitors of the enzyme dipeptidyl peptidase (DPP)-4 have been developed to treat diabetes. The enzyme DPP-4 cleaves incretins, which, among other functions, stimulate insulin and suppresses glucagon. Inhibition of this enzyme results in an increase in the half-life and the sustained physiologic action of incretins, leading to an improvement in hyperglycemia. One such agent, namely sitagliptin (MK-04,310), has been introduced into the United States market, and another agent, vildagliptin (LAF237), is being used in Europe and elsewhere. This article is intended to evaluate the effectiveness of DPP-4 inhibitors as a therapeutic modality for managing type 2 diabetes. The authors conducted a literature search of various databases to identify the clinical trials involving the DPP inhibitors and concluded that the DPP-4 inhibitors, for example, sitagliptin and vildagliptin, are efficacious for managing diabetes as monotherapy or combination therapy.