Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes

Authors

  • Xiaodan Zhang,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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  • William S. Harmsen,

    1. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Mayo Clinic Cancer Center, Rochester, MN
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  • Teresa A. Mettler,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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  • W. Ray Kim,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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  • Rosebud O. Roberts,

    1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, MN
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  • Terry M. Therneau,

    1. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Mayo Clinic Cancer Center, Rochester, MN
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  • Lewis R. Roberts,

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
    • Address reprint requests to: Lewis R. Roberts, M.B., Ch.B., Ph.D., Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905. E-mail: roberts.lewis@mayo.edu; fax: 507-284-0762.

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  • Roongruedee Chaiteerakij

    1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
    2. Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
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  • Potential conflict of interest: Nothing to report.

  • This work was supported by National Institutes of Health (NIH; grant nos.: CA128633 and CA165076; to L.R.R.), the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567), the Mayo Clinic Cancer Center (CA15083), and the Mayo Clinic Center for Clinical and Translational Science (NIH/NCRR CTSA grant no.: UL1 TR000135). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

  • See Editorial on Page 1818

Abstract

The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment. This study investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with diabetes. Diabetic patients diagnosed with cirrhosis between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were identified (n = 250). Data were retrospectively abstracted from the medical record. Survival of patients who continued versus discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox's proportional hazards analysis. Overall, 172 patients continued metformin whereas 78 discontinued metformin. Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11.8 vs. 5.6 years overall, P < 0.0001; 11.8 vs. 6.0 years for Child A patients, P = 0.006; and 7.7 vs. 3.5 years for Child B/C patients, P = 0.04, respectively). After adjusting for other variables, continuation of metformin remained an independent predictor of better survival, with an HR of 0.43 (95% CI: 0.24-0.78; P = 0.005). No patients developed metformin-associated lactic acidosis during follow-up. Conclusion: Continuation of metformin after cirrhosis diagnosis reduced the risk of death by 57%. Metformin should therefore be continued in diabetic patients with cirrhosis if there is no specific contraindication. (Hepatology 2014;60:2007–2015)

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