Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression

Purpose Metformin may have a role in reducing the incidence of colorectal cancer (CRC) and improving survival outcome. This meta-analysis explored the effect of metformin use on colorectal adenoma and cancer incidence, and colorectal oncological outcomes. Methods A database search was conducted on Medline, Embase and CNKI for studies comparing metformin vs. non-metformin users, metformin users vs. non-diabetics and metformin users vs. diabetics with diet-only treatment. Meta-analysis was done with DerSimonian and Laird with risk ratios (RR), and hazard ratios (HR) for survival outcomes. Results We included 58 studies and summarized incidences of colorectal adenoma and cancer, as well as cancer survival outcomes. Metformin users had a significant lower incidence of colorectal adenoma (RR 0.77, CI 0.67-0.88,p < 0.001), advanced adenoma (0.61, CI 0.42-0.88,p = 0.008) and CRC (RR 0.76, CI 0.69-0.84,p < 0.001) respectively compared with non-metformin users. Overall survival (HR 0.6, CI 0.53-0.67,p < 0.001) and CRC-specific survival (HR 0.66, CI 0.59-0.74,p < 0.001) were higher among metformin users compared with non-metformin users. Further analysis on overall survival of metastatic CRC patients revealed significantly higher survival rates in metformin users (HR 0.77, CI 0.68-0.87,p < 0.001). Conclusion This meta-analysis showed that metformin use significantly reduces colorectal adenoma and cancer incidence and improves colorectal cancer outcomes.