Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study

Clin Exp Pharmacol Physiol. 2008 Aug;35(8):895-903. doi: 10.1111/j.1440-1681.2008.04920.x. Epub 2008 Mar 13.


1. Metabolic syndrome (MS) is one of the greatest public health problems in Mexico, where more than 75% of adults in urban populations are overweight or obese. Metabolic syndrome has several comorbidities, which result in a high cardiometabolic risk. 2. Some of the vasopathogenic phenomena in MS are caused by nitroxidant stress, secondary to cardiometabolic dysfunction. 3. The action of metformin to diminish or control MS remains a matter of debate. 4. In the present study, 60 patients with at least three diagnostic criteria for MS were divided into two groups. Both groups received similar dietary counselling, but one group was given 850 mg metformin daily. 5. The variables assessed were body mass index, waist circumference, systolic and diastolic blood pressures (SBP and DBP, respectively), total cholesterol (TC), high- and low-density lipoprotein-cholesterol, triglycerides (TG), fasting glucose, nitroxidant metabolites (free carbonyls, malondialdehyde, dityrosines and advanced oxidative protein products (AOPP)), nitric oxide (NO), carotid vascular stiffness, carotid intima-media thickness (IMT) and C-reactive protein (CRP). 6. After 1 year follow up, both groups reported weight loss, as well as decreases in waist circumference, SBP and DBP. 7. Patients on metformin exhibited reductions in TC and IMT and there were marked changes in nitroxidation: levels of carbonyls, dityrosines and AOPP were reduced, whereas those of NO were increased, indicating better endothelial function. In addition, in patients given metformin, CRP levels decreased. 8. In conclusion, metformin has a considerable beneficial effect on nitroxidation, endothelial function and IMT in patients with MS.

Publication types

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

MeSH terms

  • Adult
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Carotid Arteries / pathology
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology
  • Metformin / therapeutic use*
  • Middle Aged
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress
  • Tunica Intima / pathology*


  • Hypoglycemic Agents
  • Nitric Oxide
  • N,N-dimethylarginine
  • Metformin
  • Arginine
  • Nitric Oxide Synthase Type III