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

Abstract

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.