Continuation of metformin use after a diagnosis of cirrhosis significantly improved survival of patients with type II diabetes (DM)
Xiaodan Zhang1, Teresa Mettler1, William S. Harmsen2, W. Ray Kim1, Terry Therneau2, Lewis R. Roberts1, Roongruedee Chaiteerokij1
1 Division of Gastroenterology ond Hepatology, College of Medicine, Mayo Clinic, Rochester, MN; 2Department of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic and Mayo Clinic Cancer Center, Rochester, MN
Background: It has been suggested that metformin use reduces the risk of hepatocellular carcinoma in cirrhotic patients with DM. However, metformin is often discontinued after the diagnosis of cirrhosis due to concerns about adverse effects in patients with liver impairment. We investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with DM. Aims: To compare survival of diabetic patients who continued metformin versus those who discontinued metformin after cirrhosis diagnosis. Methods: Diabetic patients in whom cirrhosis was diagnosed between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were enrolled and their medical records were abstracted. Survival of those who continued metformin versus those who discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox Proportional Hazards analysis. Results: 〇f the 250 patients on metformin at the time of cirrhosis diagnosis, 172 continued metformin while 78 discontinued metformin. Age, gender and baseline liver function were comparable between the 2 groups. Reasons for discontinuation of metformin were: diagnosis of cirrhosis (n=o1); uncontrolled plasma glucose (n=5); elevated serum creatinine (n=3); diarrhea, well controlled plasma glucose level, switch to insulin therapy, unstated reasons during hospitalization (n=2 for each), and heart disease (n=1). Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11. 8 vs. 5. 6 years, p<0.001) with 5 year-survival rates of 77. 5% vs. 55. 2%, respectively. By univariate analysis, continuation of metformin and high serum albumin level were significantly associated with better survival, whereas older age, increased Model for EndStage Liver Disease (MELD) score and increased serum AFP level were significantly associated with worse survival. Etiology of cirrhosis was also associated with survival. After adjusting for age, gender, albumin, MELD score and AFP level and etiology of cirrhosis, continuation of metformin was an independent predictor of better survival (HR 0.43, 95%CI 0.240.78, P<0.001). Conclusion: Continuation of metformin after cirrhosis diagnosis significantly reduced the risk of death by 57% and was significantly associated with better survival of patients with DM. Therefore, metformin should be considered in cirrhotic patients with DM if there is no specific contraindication. Validation of these results in a larger cohort is needed.
W. Ray Kim - Advisory Committees or Review Panels: Salix; Consulting: Bristol Myers Squibb, Gilead
Lewis R. Roberts - Advisory Committees or Review Panels: Inova; Grant/Research Support: Bristol Myers Squibb, Bayer, Nordion; Speaking and Teaching: Nordion
The following people have nothing to disclose: Xiaodan Zhang, Teresa Mettler, William S. Harmsen, Terry Therneau, Roongruedee Chaiteerakij