Effect of pioglitazone versus metformin on cardiovascular risk markers in type 2 diabetes

Stefano Genovese, Giorgia De Berardis, Antonio Nicolucci, Edoardo Mannucci, Virgilio Evangelista, Licia Totani, Fabio Pellegrini, Antonio Ceriello

Research output: Contribution to journalArticlepeer-review


Introduction: Besides its critical role in metabolic homeostasis, peroxisome proliferator-activated receptor (PPAR)- modulates several cellular responses involved in atherothrombosis. This multicenter, double-blind, randomized study investigated the effects of two oral hypoglycemic agents on markers of inflammation, platelet activation, thrombogenesis, and oxidative stress in patients with type 2 diabetes. Methods and Results: The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin. Additionally, markers of vascular inflammatory response, platelet activation, thrombogenesis, oxidative stress, glucose, and lipid metabolism, as well as liver function, were measured. In total, 50 patients completed the study. Pioglitazone- treated patients were found to have statistically significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to those treated with metformin (-0.2 mg/dL) (P = 0.04), as well as greater reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P = 0.01), serum insulin (-2 vs. -1.9 mU/L; P = 0.014), homeostatic model assessment (HOMA) (-1.2 vs. -0.9; P = 0.015), and E-selectin (-12.4 vs. +3.4 μg/mL; P = 0.01). Mean glycated hemoglobin (HbA1c) levels decreased in both treatment groups from baseline to week 16 (-0.4% in the pioglitazone group, -0.2% in the metformin group; P = 0.36). Pioglitazone treatment was also found to be associated with a statistically significant increase in total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the metformin arm; P = 0.05) and a decrease in liver enzyme levels. Conclusions: The favorable changes in markers of systemic and vascular inflammatory response with pioglitazone suggest that it may positively influence the atherothrombotic process in type 2 diabetes.

Original languageEnglish
Pages (from-to)190-202
Number of pages13
JournalAdvances in Therapy
Issue number2
Publication statusPublished - 2013


  • Cardiovascular disease
  • Cardiovascular risk factors
  • Metformin
  • Oral pharmacologic agents
  • Pioglitazone
  • Type 2 diabetes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Medicine(all)


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