Impact of Metformin Use on Risk and Mortality of Hepatocellular Carcinoma in Diabetes Mellitus

Background: The views regarding the associations between metformin use and hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients are divisive. Thus we summarized all available published studies evaluating the relationship between metformin therapy and HCC survival and risk, and aim to conduct an updated meta-analysis study to more accurately clarify the association.

Methods: We searched for articles regarding impact of metformin use on risk and mortality of HCC in DM and published before April 2021 in databases (PubMed and Web of Science). We used STATA 12.0 software to compute odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) to generate a computed effect size and 95% CI.

Results: The present study showed that metformin use was associated with a decreased risk of HCC in DM with a random effects model (OR/RR = 0.59, 95% CI 0.51-0.68, I2 = 96.5%, p < 0.001). In addition, the study indicated that metformin use was associated with a decreased all-cause mortality of HCC in DM with a random effects model (HR = 0.74, 95% CI 0.66-0.83, I2 = 49.6%, p = 0.037).

Conclusion: In conclusion, our studies support that the use of metformin in DM patients is significantly associated with reduced risk and all-cause mortality of HCC. And more prospective studies focusing on the metformin therapy as a protective factor for HCC are needed to verify the accuracy of the findings.