title: Lymphocyte-suppressing and systemic anti-inflammatory effects of high-dose metformin in simvastatin-treated patients with impaired fasting glucose.
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.
authors.affiliation: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland. r.krysiak@interia.pl
authors.forename: Robert
authors.initials: R
authors.lastname: Krysiak
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Okopien
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004357:Drug Synergism; D005215:Fasting / Q000097:blood*; D005260:Female; D044882:Glucose Metabolism Disorders / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011044:Poland; D019821:Simvastatin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; C573420:ICAM1 protein, human; D018836:Inflammation Mediators; D008055:Lipids; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D008687:Metformin; D019821:Simvastatin