title: Monocyte-suppressing effect of high-dose metformin in fenofibrate-treated patients with impaired glucose tolerance.
abstract: BACKGROUND
  Fibrates were found to reduce cytokine release and low-grade inflammation in patients with impaired glucose tolerance. The aim of this study was to investigate whether these effects of fibrates may be potentiated by metformin treatment.
  
  
  METHODS
  The study included 43 patients with isolated impaired glucose tolerance and normal plasma lipids who had been treated for at least 6 months with micronized fenofibrate (200 mg daily). These subjects were randomly assigned to 12 weeks' treatment with either high dose metformin (3 g daily in three divided doses) or placebo. Plasma lipids, glucose homeostasis markers, monocyte cytokine release and plasma C-reactive protein levels were determined before randomization and at the end of the treatment.
  
  
  RESULTS
  Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor-α and interleukin-6, as well as tended to reduce monocyte release of interleukin-1β and monocyte chemoattractant protein-1, which was accompanied by an improvement in insulin sensitivity.
  
  
  CONCLUSIONS
  Our results show that high-dose metformin produces monocyte-suppressing and systemic anti-inflammatory effects in fibrate-treated patients with isolated impaired glucose tolerance. This suggests that fibrate-metformin combination therapy may bring clinical benefits to impaired glucose tolerance patients at high cardiovascular risk.
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: Anna
authors.initials: A
authors.lastname: Gdula-Dymek
authors.forename: Bogusław
authors.initials: B
authors.lastname: Okopień
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011044:Poland; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D008055:Lipids; D002097:C-Reactive Protein; D008687:Metformin; D011345:Fenofibrate