The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha

Gian Paolo Fadini, Elisa Boscaro, Mattia Albiero, Lisa Menegazzo, Vera Frison, Saula de Kreutzenberg, Carlo Agostini, Antonio Tiengo, Angelo Avogaro, Gian Paolo Fadini, Elisa Boscaro, Mattia Albiero, Lisa Menegazzo, Vera Frison, Saula de Kreutzenberg, Carlo Agostini, Antonio Tiengo, Angelo Avogaro

Abstract

Objective: Vasculoprotective endothelial progenitor cells (EPCs) are regulated by stromal-derived factor-1alpha (SDF-1alpha) and are reduced in type 2 diabetes. Because SDF-1alpha 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-1alpha, 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-1alpha and a decrease in MCP-1.

Conclusions: Sitagliptin increases circulating EPCs in type 2 diabetic patients with concomitant upregulation of SDF-1alpha. This ancillary effect of DPP-4 inhibition might have potential favorable cardiovascular implications.

Trial registration: ClinicalTrials.gov NCT00968006.

Figures

Figure 1
Figure 1
Effects of sitagliptin on DPP-4 activity, progenitor cells, and soluble factors. Plasma free DPP-4 activity (A), CD34+KDR+ EPCs levels (B), CD34+ cell levels (C), and concentrations of SDF-1α (D), MCP-1 (E), and VEGF (F) were determined at baseline and at 4 weeks in the sitagliptin intervention group and in the control group. *P < 0.05.

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