title: Vascular protection with dipeptidyl peptidase-IV inhibitors in diabetes: experimental and clinical therapeutics.
abstract: The dipeptidyl peptidase-IV (DPP-IV) inhibitors, also known as gliptins, are widely used in clinical practice either as monotherapy or in combination with other agents for the management of type 2 diabetes mellitus (T2DM). The gliptins are effective, safe, well tolerated, and conveniently administered once/day. Moreover, these agents have a low risk for drug interactions and do not require initial dosage titrations to lessen adverse effects. They are not only clinically desirable, having the most favorable side-effect profile of all available antihyperglycemic medications, but they can also be used in any stage of renal or hepatic impairment. The antihyperglycemic effects of gliptins are attributed to inhibition of the DPP-IV enzyme, thereby prolonging the half-life (t1/2 ) of incretin hormones (substrates) to promote glucose-stimulated insulin secretion. Beyond their glucose-lowering effects, gliptins may also reduce the risk of cardiovascular disease by improving endothelial function, lowering blood pressure, reducing inflammation, and delaying the progression of atherosclerosis. Although the vascular protective effects of gliptins depend on incretins, the contributions of other biologically important endogenous vasoactive substrates of DPP-IV are worthy of consideration from a therapeutic standpoint. Future and ongoing studies should help determine whether these vascular protective effects contribute to improved cardiovascular outcomes in patients with T2DM. The experimental and clinical evidence supporting the vascular protective effects of gliptins is reviewed.
authors.affiliation: Program in Clinical and Experimental Therapeutics, Department of Clinical and Administrative Pharmacy and Division of Experience Programs, College of Pharmacy, University of Georgia, Augusta, Georgia; Center for Pharmacy and Experimental Therapeutics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: Heba A
authors.initials: HA
authors.lastname: Ahmed
authors.forename: Dianne W
authors.initials: DW
authors.lastname: May
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Lakshman
authors.initials: L
authors.lastname: Segar
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D014652:Vascular Diseases / Q000201:enzymology / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D002316:Cardiotonic Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
keywords: DPP-IV inhibitors; clinical evidence; clinical studies; dipeptidyl peptidase-IV inhibitors; experimental evidence; gliptins; incretins; type 2 diabetes mellitus; vascular protection