Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis.

Abstract

Data on the potential effect of metformin on the risk of liver cancer are limited and inconsistent. The objective of this study was to review the evidence currently available to examine the potential role of metformin in chemoprevention for liver cancer in patients with type 2 diabetes. The data sources of the study included the PubMed and SciVerse Scopus databases. Selection included studies that assessed the effect of metformin therapy on the risk of liver cancer in patients with type 2 diabetes. Summary effect estimates were derived using a random-effects meta-analysis model. A database was developed on the basis of five studies consisting of approximately 105,495 patients with type 2 diabetes. In meta-analyses, metformin was associated with an estimated 62% reduction in the risk of liver cancer among patients with type 2 diabetes (odds ratio 0.38, 95% confidence interval 0.24, 0.59; P < 0.001). The effect estimates were heterogeneous across the five included studies (P for heterogeneity = 0.001; I(2) = 78%). When restricting the analysis to the four studies related to hepatocellular carcinoma, metformin was again associated with a significantly lower cancer risk (odds ratio 0.30, 95% confidence interval 0.17, 0.52; P < 0.001), and there was evidence of significant heterogeneity between these four studies (P for heterogeneity = 0.03; I(2) = 67%). Metformin appears to be associated with a lower risk of liver cancer in patients with type 2 diabetes. Further investigation, including mechanistic studies, well-designed cohort studies, and possibly controlled trials, is needed.