Long-Term Treatment With Sitagliptin Provides Multiple Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics With Stable Coronary Artery Disease

Introduction: Diabetes mellitus (DM) is thought to be highly involved in complex atherothrombogenic processes, but the long-term antiatherosclerotic therapies in patients with type-2 DM have not been established. Hypothesis: Therefore we assessed hypothesis long-term treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor recently developed antidiabetic agent, chronically inhibits atherosclerotic progression in patients with type-2 DM. Methods: Thirty-two type-2 diabetic patients with stable coronary artery disease were randomized to group-S where they received sitagliptin (50mg/day), or to group-C where they received enhanced antidiabetic therapy without a dipeptidyl peptidase-4 inhibitor for 2 years. We quantified flow-mediated endothelium-dependent dilation of right brachial artery after 5 minutes forearm occlusion (FMD), and intima-media thickness of common carotid artery (IMT) using high-resolution ultrasonography. We also quantified brachial-to-ankle pulse wave velocity (PWV). Changes in FMD, IMT, PWV, and practical metabolic variables were compared between the two study groups. Results: The patients in group-S (n=16) manifested good compliance to the long-term treatment and improvements in diabetic and lipid variables represented by HbA1c and LDL after long-term medication of sitagliptin, while there were no improvements in group-C. FMD improved after medication in group-S (from 3.9±1.8% to 6.4±2.6%, p Conclusions: This study suggests that long-term treatment of sitagliptin safely improves arterial function independent of reversal for diabetic status and reduces progression of wall thickness, which may have potential benefit for long-term management of atherosclerosis in type-2 diabetics with stable coronary artery disease.