Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34 + CXCR4 + cells in patients with type 2 diabetes

Abstract

We investigated the effects of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on the number of circulating CD34⁺CXCR4⁺cells, a candidate for endothelial progenitor cells (EPCs), plasma levels of stromal cell-derived factor (SDF)-1α, a ligand for CXCR4 receptor and a substrate for DPP-4, and plasma levels of interferon-inducible protein (IP)-10, for a substrate for DPP-4, in patients with type 2 diabetes. We studied 30 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. Thirty diabetic patients were randomized in a 2:1 ratio into a sitagliptin (50 mg/day) treatment group or an active placebo group (glimepiride 1 mg/day) for 12 weeks. Both groups showed similar improvements in glycemic control. The number of circulating CD34⁺CXCR4⁺ cells was increased from 30.5 (20.0, 47.0)/10⁶ cells at baseline to 55.5 (31.5, 80.5)/10⁶ cells at 12 weeks of treatment with 50 mg/day sitagliptin (P = 0.0014), while showing no significant changes in patients treated with glimepiride. Plasma levels of SDF-1α and IP-10, both physiological substrates of endogenous DPP-4 and chemokines, were significantly decreased at 12 weeks of sitagliptin treatment. In conclusion, treatment with sitagliptin increased the number of circulating CD34⁺CXCR4⁺ cells by approximately 2-fold in patients with type 2 diabetes.

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