title: Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality.
abstract: OBJECTIVE
  Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.
  
  
  METHODS
  The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.
  
  
  RESULTS
  Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.
  
  
  CONCLUSIONS
  Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00325910.
authors.affiliation: School of Public Health, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada. deurich@ualberta.ca
authors.forename: Dean T
authors.initials: DT
authors.lastname: Eurich
authors.forename: Ross T
authors.initials: RT
authors.lastname: Tsuyuki
authors.forename: Sumit R
authors.initials: SR
authors.lastname: Majumdar
authors.forename: Finlay A
authors.initials: FA
authors.lastname: McAlister
authors.forename: Richard
authors.initials: R
authors.lastname: Lewanczuk
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Shibata
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta; D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004348:Drug Labeling; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D018579:Patient Selection; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin