Dipeptidyl Peptidase‐4 Inhibitors Attenuate Endothelial Function as Evaluated by Flow‐Mediated Vasodilatation in Type 2 Diabetic Patients

Background Endothelial dysfunction is an independent predictor for cardiovascular events in patients with type 2 diabetes (T2DM). Glucagon like peptide‐1 (GLP‐1) reportedly exerts vasodilatory actions, and inhibitors of dipeptidyl peptidase‐4 (DPP‐4), an enzyme‐degrading GLP‐1, are widely used to treat T2DM. We therefore hypothesized that DPP‐4 inhibitors (DPP‐4Is) improve endothelial function in T2DM patients and performed 2 prospective, randomized crossover trials to compare the DPP‐4I sitagliptin and an α‐glucosidase inhibitor, voglibose (in study 1) and the DPP‐4Is sitagliptin and alogliptin (in study 2). Methods and Results In study 1, 24 men with T2DM (46±5 years) were randomized to sitagliptin or voglibose for 6 weeks without washout periods. Surprisingly, sitagliptin significantly reduced flow‐mediated vasodilatation (FMD; −51% compared with baseline, P