Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients.

Abstract

Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes. We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables. In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12months of treatment. A group of 16 compensated diabetics served as controls. The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P<0.05) greater in the S-treated patients. In the S-group glucose metabolism and FMD significantly improved during the follow-up (from 169.3±8 to 157.1±9mg/dl, P<0.05, from 7.9±0.1 to 6.9±0.2%, P<0.001 and from 3.6±0.3 to 7.4±0.8%, respectively P<0.05). No significant difference was detected in the other parameters, including blood pressure. Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.