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

J Clin Endocrinol Metab. 2012 Jul;97(7):2347-53. doi: 10.1210/jc.2012-1267. Epub 2012 Apr 20.


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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Algorithms
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / prevention & control*
  • Chemoprevention / methods
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Liver Neoplasms / complications
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / prevention & control*
  • Metformin / therapeutic use*


  • Hypoglycemic Agents
  • Metformin