Abstract 9876: Long-Term Treatment With Sitagliptin Provides Multiple Ultrasonic Manifested Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics

Background: Diabetes mellitus is thought to be highly involved in complex atherothrombogenic processes, but the long-term antiatherosclerotic therapies in patients with type-2 diabetes mellitus have not been established. We previously demonstrated adverse prognostic impacts of endothelial dysfunction and intima-media thickening.

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 diabetes mellitus.

Methods: Thirty-four 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 transient forearm occlusion (FMD), endothelium-independent dilation of brachial artery after sublingual administration of nitroglycerin (TNG), and intima-media thickness of common carotid artery (IMT) using high-resolution ultrasonography. Changes in FMD, TNG, and IMT were compared between the two groups.

Results: Group-S (n=17) 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 4.0±1.9% to 6.3±2.7%, p<0.01) but not in group-C (from 4.1±2.0% to 4.0±1.9%, p=0.78). Changes of FMD in group-S did not correlate to those of HbA1c (r= 0.14, p=0.57). TNG (%) remained unchanged in both group-S and group-C. IMT did not increase in group-S (from 1.10±0.35mm to 1.08±0.40mm, p=0.17) but increased in group-C (from 1.09±0.47mm to 1.17±0.48mm, p<0.01).

Conclusion: This ultrasonic study suggests that long-term treatment of sitagliptin safely improves endothelial function of brachial artery independent of reversal for diabetic status and reduces progression of wall thickness in carotid artery, which may have beneficial potentials for long-term management of atherosclerosis in type-2 diabetics.