Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes

Abstract

Background: Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown.

Methods: Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34⁺/CD133⁺/KDR⁺/10⁶ cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed.

Results: Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers.

Conclusions: V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013.

Keywords: Cardiovascular risk; DPP-4 inhibitors; EPC; SDF-1α.

Fig. 1

EPC number evaluation. Flow-cytometry analysis scatter plots to assess EPC number. Within the lymphomonocyte population (a) CD34 (b) and CD133 (c) positive cells were gated and evaluated for the expression of KDR to identify CD34⁺/CD133⁺/KDR⁺ cells (d)

Fig. 2

Consort flow chart. The figure shows the consort flow chart according to ITT analysis

Fig. 3

Treatment effect. The figure displays the treatment effect (β-coefficient and SE) of vildagliptin (treating glibenclamide as reference group) on EPC number (a) and SDF-1α levels (b) in repeated measure GLM models after adjustment for baseline values. (*p < 0.05; **p < 0.01)