Lymphocyte-suppressing and systemic anti-inflammatory effects of high-dose metformin in simvastatin-treated patients with impaired fasting glucose

Atherosclerosis. 2012 Dec;225(2):403-7. doi: 10.1016/j.atherosclerosis.2012.09.034. Epub 2012 Oct 12.

Abstract

Objective: No previous study has investigated whether metformin produces any effect on lymphocyte secretory function in patients with glucose metabolism abnormalities.

Methods: Sixty-two subjects with impaired fasting glucose (IFG) treated for at least 3 months with simvastatin were allocated into one of two groups receiving, respectively, metformin (3 g daily) or placebo for the following 90 days. Plasma lipids, glucose homeostasis markers, plasma C-reactive protein and intercellular adhesion molecule-1 levels, as well as lymphocyte release of proinflammatory cytokines were determined before randomization and at the end of the treatment.

Results: Fifty-eight patients completed the study. Metformin, but not placebo, administered to simvastatin-treated IFG subjects reduced plasma levels of C-reactive protein, soluble intercellular adhesion molecule-1, as well as lymphocyte release of interleukin-2, interferon-γ and tumor necrosis factor-α, which was accompanied by the improvement in insulin sensitivity and a reduction in free fatty acid levels.

Conclusions: The obtained results indicate that metformin potentiates lymphocyte-suppressing and systemic anti-inflammatory effects of simvastatin in subjects with IFG. These effects of statin-metformin combination therapy may play a role in the prevention and treatment of atherosclerosis and its complications in patients with early glucose metabolism abnormalities.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage*
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • C-Reactive Protein / metabolism
  • Cytokines / blood
  • Drug Synergism
  • Fasting / blood*
  • Female
  • Glucose Metabolism Disorders / blood
  • Glucose Metabolism Disorders / drug therapy*
  • Glucose Metabolism Disorders / immunology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hypoglycemic Agents / administration & dosage*
  • Inflammation Mediators / blood
  • Intercellular Adhesion Molecule-1 / blood
  • Lipids / blood
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Poland
  • Simvastatin / administration & dosage*
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Blood Glucose
  • Cytokines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypoglycemic Agents
  • ICAM1 protein, human
  • Inflammation Mediators
  • Lipids
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • Metformin
  • Simvastatin