The pleiotropic cardiovascular effects of dipeptidyl peptidase-4 inhibitors.

Patients with Type 2 diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the guidelines for the management of Type 2 diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors, also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 (GLP-1): this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. In addition to incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y and peptide YY. In this review, we will discuss the pathophysiological relevance of gliptin pleiotropism and its translational potential.