Effects of pioglitazone versus metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes--a randomized controlled trial

Diabetes Obes Metab. 2011 May;13(5):439-45. doi: 10.1111/j.1463-1326.2011.01367.x. Epub 2011 Jan 21.


Aim: Endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are markers of endothelial injury and repair. We compared the effects of pioglitazone versus metformin on the circulating numbers of EMPs and EPCs in patients with newly diagnosed type 2 diabetes.

Methods: This was a randomized, double-blind, comparator-controlled, 24-week single-centre trial conducted in a Teaching Hospital in Naples, Italy. One hundred and ten people with newly diagnosed type 2 diabetes who were never treated with antihyperglycaemic drugs and had haemoglobin A1c (HbA1c) levels between 7 and 10% were given pioglitazone hydrochloride (15-45 mg/day) (n = 55) or metformin (1000-2000 mg/day) (n = 55) as an active comparator. Absolute change from baseline to final visit in circulating EMPs and EPCs and their ratio were the main outcomes.

Results: Baseline characteristics did not differ between the study groups. The decrease in circulating EMPs CD31+ [intergroup difference, -32 counts/µl (95% CI -51 to -9)] and the increase in EPCs CD34+/KDR+ [intergroup difference, 33 cells/10(6) events (95% CI 13 to 55)] were greater with pioglitazone versus metformin. EMPs/EPCs ratio was reduced with pioglitazone and unchanged with metformin [difference, -1.5 (95% CI -2.6 to -0.5), p < 0.001]. Participants assigned to pioglitazone gained more weight and experienced greater improvements in some coronary risk measures [high-density lipoprotein (HDL)-cholesterol, triglycerides, adiponectin and C-reactive protein (CRP)] than did those assigned to metformin.

Conclusion: Compared with metformin, pioglitazone treatment improved the imbalance between endothelial damage and repair capacity and led to more favourable changes in coronary risk factors in patients with newly diagnosed type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Cell Survival / drug effects
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / prevention & control*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / prevention & control*
  • Double-Blind Method
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Italy / epidemiology
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Pioglitazone
  • Stem Cells / drug effects
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / therapeutic use*


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Metformin
  • Pioglitazone