Abstract
BackgroundFewer 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.MethodsRandomized (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.ResultsBaseline 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.ConclusionsV 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
Highlights
Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cellderived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality
Recent evidence points to a potential role of dipeptidyl peptidase-4 inhibitors (DPP-4i) in increasing circulating EPC number
A subsequent study investigated the mid-term effects of sitagliptin in boosting EPC levels, but the reported results may be potentially attributable to a regression to the mean effect [11]
Summary
We conducted a randomized (2:1), open-label activetreatment-controlled clinical trial (NCT01822548) to compare the effects of vildagliptin (V) (100 mg/daily) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC and (C-term) SDF-1∝ levels at 4 and 12 months of treatment. Circulating pro-inflammatory chemokine/cytokine profile [C-reactive protein (CRP), IL-6, TNF-∝], brain natriuretic peptide (BNP), total GLP-1, (C-term) SDF-1∝ and EPC number were assessed. Circulating EPCs (expressed as number of CD133+/CD34+/KDR+ cells/106 total cytofluorimetric events) were acquired in a FACSCantoII cytometer and analysed using FACSDiva software (both by BD Biosciences). Sample size determination Sample size was calculated to achieve 80% power to reject the null hypothesis of equal mean changes in the primary endpoint when the population mean difference is 0.15 with a standard deviation of 0.2 in both groups and with a significance level (∝) of 0.05 using a two-sided twosample equal-variance t test (difference between the two treatments at 12 months) (software PASS- NCSS, USA). Statistical analysis was performed using SPSS v. 22 (IBM Statistics)
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