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 pa- tients 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 90 d 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) of 1.1 (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.