CONTEXT: Data on the potential effect of metformin on the risk of liver cancer are limited and inconsistent. OBJECTIVE: 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. DATA SOURCES: The data sources of the study included the PubMed and SciVerse Scopus databases. STUDY SELECTION: Selection included studies that assessed the effect of metformin therapy on the risk of liver cancer in patients with type 2 diabetes. DATA EXTRACTION: Summary effect estimates were derived using a random-effects meta-analysis model. DATA SYNTHESIS: 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%). CONCLUSIONS: 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.
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