Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review.

.: Preventive effect of metformin in hepatocellular carcinoma (HCC) is not entirely clear. We aimed to evaluate the use of metformin as a protective factor of HCC in diabetic patients. .: We carried out an electronic search on PUBMED/MEDLINE, Web of Science and LILACS databases, with no limit of date, from April 2017 to January 2019. Eligible studies included cohort and case-control studies. We adressed data about the use of metformin on the risk of HCC development. Two independent reviewers extracted the data. We evaluated the quality of studies by using the Newcastle-Ottawa scale and carried out a meta-analysis using random-effects models. .: The electronic searches identified 747 studies. After reading abstracts and titles, we excluded 327 duplicated papers and 383 irrelevant references. Eight studies were selected; four case-control and four cohort studies. All studies have observed that the therapy with metformin was associated with a lower risk of HCC, compared with non-metformin therapy. Five articles reported that patients treated with insulin, or insulin secretagogues, presented increased risk of HCC compared to those treated with metformin. One study found that not only statin but also aspirin reduced the risk of HCC, if combined with metformin. A meta-analysis, using the case-control studies, found a combined Odds Ratio of 0.468; 95% CI 0.275-0.799 for the association between HCC and the use of metformin. .: The use of metformin was associated with a reduced risk of HCC, and it may be a relevant factor for preventing HCC in diabetic patients.