Metformin does not improve survival in patients with hepatocellular carcinoma

AIM:To assess whether metformin,which has a chemopreventive effect in chronic liver disease,has any chemotherapeutic effect in hepatocellular carcinoma.METHODS:This was a retrospective study of 701 patients with newly diagnosed hepatocellular carcinoma(HCC)seen between January 2005 and June 2011 at Mayo Clinic,Rochester,Minnesota.This patient cohort was a part of the global HCC BRIDGE study,which is a large longitudinal study of HCC determining the realworld experience of HCC characteristics,management and patient outcomes.We defined significant metformin exposure as continuation of this agent at least 90d beyond diagnosis of HCC,and compared survival of diabetic patients on metformin to diabetic patients not on metformin and non-diabetics.RESULTS:Our cohort was 72.9%male,with a mean±SD age of 62.6±12.3 years.The most common etiologies of liver disease were hepatitis C(34%),alcoholic liver disease(29%),fatty liver disease(15%)and hepatitis B(9%).By univariate analysis,using diabetics not on metformin as the reference group,diabetic patients with HCC on metformin had no survival advantage,with a HR(95%CI)of 1.0(0.8-1.3).Non-diabetic HCC patients also did not appear to have a survival advantage as compared to diabetic HCC patients not on metformin,as demonstrated by a HR(95%CI)of1.1(0.7-1.7).Diabetics on metformin beyond 90 d after HCC diagnosis had a longer median survival at 34.2 mo,as compared to 25.5 mo among diabetic patients who were not on metformin or had discontinued metformin within 90 d after HCC diagnosis.This finding was likely due to potential survival bias among those who lived long enough to receive metformin.CONCLUSION:Although the literature suggests a chemotherapeutic effect in other malignancies,our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC.