The Oral Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Increases Circulating Endothelial Progenitor Cells in Patients With Type 2 Diabetes Possible role of stromal-derived factor-1α

OBJECTIVE - Vasculoprotective endothelial progenitor cells (EPCs) are regulated by stromal-derived factor-1 alpha (SDF-1 alpha) and are reduced in type 2 diabetes. Because SDF-1 alpha is a substrate of dipeptidyl-peptidase-4 (DPP-4), we investigated whether the DPP-4 inhibitor sitagliptin modulates EPC levels in type 2 diabetic patients. RESEARCH DESIGN AND METHODS - This was a controlled, nonrandomized clinical trial comparing 4-week sitagliptin (n = 16) versus no additional treatment (n = 16) in addition to metformin and/or secretagogues in type 2 diabetic patients. We determined circulating EPC levels and plasma concentrations of SDF-1 alpha, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and nitrites/nitrates. RESULTS - There was no difference in clinical baseline data between the sitagliptin and control arms. After 4 weeks, as compared with control subjects, patients receiving sitagliptin showed a significant increase in EPCs and SDF-1 alpha and a decrease in MCP-1. CONCLUSIONS - Sitagliptin increases circulating EPCs in type 2 diabetic patients with concomitant upregulation of SDF-1 alpha. This ancillary effect of DPP-4 inhibition might have potential favorable cardiovascular implications.