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Metformin Use and Mortality Among Patients With Diabetes and Atherothrombosis

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ARCHIVES OF INTERNAL MEDICINE
卷 170, 期 21, 页码 1892-1899

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AMER MEDICAL ASSOC
DOI: 10.1001/archinternmed.2010.409

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资金

  1. Sanofi-aventis
  2. Merck Sharp et Dohme (MSD)-Chibret
  3. Servier Laboratories
  4. F. Hoffman-La Roche Ltd
  5. Eli Lilly and Company
  6. Novo Nordisk A/S
  7. Medtronic Inc
  8. Lifescan Inc
  9. Eisai Pharmaceuticals
  10. Daiichi-Sankyo Co Ltd
  11. GlaxoSmithKline plc
  12. Bristol-Myers Scribb
  13. Otsuka Pharmaceutical Group
  14. Bayer AG
  15. Schering-Plough
  16. Takeda Pharmaceutical Co Ltd
  17. Astellas Pharma Inc
  18. AstraZeneca
  19. Novartis Pharmaceuticals Corporation
  20. Kowa Company Ltd
  21. Pfizer Inc
  22. Ono Pharmaceutical
  23. MSD-Chibret
  24. Bristol-Myers Squibb
  25. Waksman Foundation of Japan, Inc

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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 60mL/min/1.73m(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.

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