Unraveling the link between metformin use and risk of hepatocellular carcinoma |
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Unraveling the link between metformin use and risk of hepatocellular carcinoma

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Metformin is a widely used insulin-sensitizing agent. It improves insulin sensitivity, reduces plasma levels of insulin, inhibits hepatic gluconeogenesis, and decreases glycogenolysis. Information available from several studies has shown an inverse relationship between the use of metformin and the risk of developing solid tumors, such as pancreatic and prostate cancer. Although experimental studies provide evidence for this drug’s chemo preventive action, its effect on hepatocellular carcinoma is not entirely clear. A systematic review assessed the use of metformin as a protective factor of hepatocellular carcinoma in patients with diabetes. An electronic search on PUBMED/MEDLINE, Web of Science, and LILACS databases was carried out, with no limit of date, from April 2017 to January 2019. The electronic searches identified 747 studies. Of these, 8 were selected (case-control:4 and cohort studies:4). All these studies observed that metformin therapy was associated with a lower risk of hepatocellular carcinoma than the non-metformin therapy group. Five articles found out that patients treated with insulin, or insulin secretagogues, were at higher risk of hepatocellular carcinoma than those treated with metformin. One study reported that if combined with metformin, both statin and aspirin decreased hepatocellular carcinoma risk. Using the case-control studies, a meta-analysis found a combined Odds Ratio of 0.468; 95% confidence interval: 0.275–0.799 for the link between the use of metformin and hepatocellular carcinoma.

Furthermore, studies conducted in the past have also shown an independent association between metformin use and reduced occurrence of hepatocellular carcinoma and liver-related mortality. According to a case-control study, 85% reduction in the chance of developing this carcinoma has been reported in cirrhotic patients who were given metformin compared to those on exogenous insulin and insulin secretagogues. Therefore, the researchers have suggested that metformin therapy may be useful for reducing the risk of hepatocellular carcinoma.


CunhaV, Pinchemel H, Rocha CR, et al. Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review.Annals of Hepatology. 2020;19(3):232-237.

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