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

Cardiovasc Diabetol. 2017 Feb 23;16(1):27. doi: 10.1186/s12933-017-0503-0.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Adamantane / therapeutic use
  • Aged
  • Cell Count / methods
  • Chemokine CXCL12 / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Endothelial Progenitor Cells / drug effects*
  • Endothelial Progenitor Cells / physiology
  • Female
  • Follow-Up Studies
  • Glyburide / pharmacology
  • Glyburide / therapeutic use*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Nitriles / pharmacology
  • Nitriles / therapeutic use*
  • Pyrrolidines / pharmacology
  • Pyrrolidines / therapeutic use*
  • Time Factors
  • Vildagliptin

Substances

  • Chemokine CXCL12
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Nitriles
  • Pyrrolidines
  • Vildagliptin
  • Adamantane
  • Glyburide

Associated data

  • ClinicalTrials.gov/NCT01822548
  • ClinicalTrials.gov/NCT01822548