title: Metformin use and mortality among patients with diabetes and atherothrombosis.
abstract: BACKGROUND
  Metformin is recommended in type 2 diabetes mellitus because it reduced mortality among overweight participants in the United Kingdom Prospective Diabetes Study when used mainly as a means of primary prevention. However, metformin is often not considered in patients with cardiovascular conditions because of concerns about its safety.
  
  
  METHODS
  We assessed whether metformin use was associated with a difference in mortality among patients with atherothrombosis. The study sample comprised 19 691 patients having diabetes with established atherothrombosis participating in the Reduction of Atherothrombosis for Continued Health (REACH) Registry between December 1, 2003, and December 31, 2004, treated with or without metformin. Multivariable adjustment and propensity score were used to account for baseline differences. The main outcome measure was 2-year mortality.
  
  
  RESULTS
  The mortality rates were 6.3% (95% confidence interval [CI], 5.2%-7.4%) with metformin and 9.8% 8.4%-11.2%) without metformin; the adjusted hazard ratio (HR) was 0.76 (0.65-0.89; P < .001). Association with lower mortality was consistent among subgroups, noticeably in patients with a history of congestive heart failure (HR, 0.69; 95% CI, 0.54-0.90; P = .006), patients older than 65 years (0.77; 0.62-0.95; P = .02), and patients with an estimated creatinine clearance of 30 to 60 mL/min/1.73 m(2) (0.64; 95% CI, 0.48-0.86; P = .003) (to convert creatinine clearance to mL/s/m(2), multiply by 0.0167).
  
  
  CONCLUSIONS
  Metformin use may decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom metformin use is not now recommended. Metformin use should be tested prospectively in this population to confirm its effect on survival.
authors.affiliation: INSERM, Department of Diabetology, Bichat Hospital, Paris, France. ronan.roussel@bch.aphp.fr
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Florence
authors.initials: F
authors.lastname: Travert
authors.forename: Blandine
authors.initials: B
authors.lastname: Pasquet
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: Sidney C
authors.initials: SC
authors.lastname: Smith
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Avi
authors.initials: A
authors.lastname: Porath
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002561:Cerebrovascular Disorders / Q000401:mortality*; D003324:Coronary Artery Disease / Q000401:mortality*; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D058729:Peripheral Arterial Disease / Q000401:mortality*; D016016:Proportional Hazards Models; D012042:Registries; D055502:Secondary Prevention
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D003404:Creatinine