Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

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; I2 = 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; I2 = 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.