title: Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.
abstract: OBJECTIVE
  Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.
  
  
  OBJECTIVE
  To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).
  
  
  METHODS
  Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.
  
  
  METHODS
  Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.
  
  
  METHODS
  The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.
  
  
  RESULTS
  At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.
  
  
  CONCLUSIONS
  Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01217307.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Chris P H
authors.initials: CP
authors.lastname: Lexis
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, the Netherlands.
authors.forename: Iwan C C
authors.initials: IC
authors.lastname: van der Horst
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lipsic
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Wouter G
authors.initials: WG
authors.lastname: Wieringa
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Ad F M
authors.initials: AF
authors.lastname: van den Heuvel
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Hindrik W
authors.initials: HW
authors.lastname: van der Werf
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Remco A J
authors.initials: RA
authors.lastname: Schurer
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Gabija
authors.initials: G
authors.lastname: Pundziute
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Eng S
authors.initials: ES
authors.lastname: Tan
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Wybe
authors.initials: W
authors.lastname: Nieuwland
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Hendrik M
authors.initials: HM
authors.lastname: Willemsen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Dorhout
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.
authors.forename: Barbara H W
authors.initials: BH
authors.lastname: Molmans
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, the Netherlands.
authors.forename: Anouk N A
authors.initials: AN
authors.lastname: van der Horst-Schrivers
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, the Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen, the Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: ter Horst
authors.affiliation: VU University, VU University Medical Center, Department of Cardiology, Amsterdam, the Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: University of Amsterdam, Academic Medical Center, Department of Cardiology, Amsterdam, the Netherlands.
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands8University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.affiliation: Department of Cardiology, Meander Medical Center, Amersfoort, the Netherlands.
authors.forename: Bart J G L
authors.initials: BJ
authors.lastname: de Smet
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D062645:Percutaneous Coronary Intervention; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin