title: Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial.
abstract: Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.
  
  
  
  This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.
  
  
  
  52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference -0.9 mmol/L, 95% CI -2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.
  
  
  
  Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.
  
  
  
  ISRCTN66148745 and NCT01247870.
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Hitchings
authors.affiliation: Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: Dilys
authors.initials: D
authors.lastname: Lai
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D019270:Fructosamine / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D019270:Fructosamine; D002097:C-Reactive Protein; D008687:Metformin
keywords: COPD Exacerbations; COPD Pharmacology