Potential conflict of interest: Nothing to report.
Liver Failure/Cirrhosis/Portal Hypertension
Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes
Article first published online: 31 JUL 2014
© 2014 by the American Association for the Study of Liver Diseases
Volume 60, Issue 6, pages 2008–2016, December 2014
How to Cite
Zhang, X., Harmsen, W. S., Mettler, T. A., Kim, W. R., Roberts, R. O., Therneau, T. M., Roberts, L. R. and Chaiteerakij, R. (2014), Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology, 60: 2008–2016. doi: 10.1002/hep.27199
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
- Issue published online: 24 NOV 2014
- Article first published online: 31 JUL 2014
- Accepted manuscript online: 3 MAY 2014 10:41AM EST
- Manuscript Accepted: 29 APR 2014
- Manuscript Received: 24 JAN 2014
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)