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Effect of metformin use on the risk and prognosis of colorectal cancer in diabetes mellitus: a meta-analysis

Supplemental Digital Content is available in the text. Whether metformin is a protective factor of colorectal cancer (CRC) among CRC patients is still not entirely clear. Thus, we conducted this systemic review and meta-analysis to provide a comprehensive review of associations between metformin therapy and CRC risk or survival outcomes for clinical decisions. Articles published before July 2021 were searched in databases (PubMed and Web of Science). Odds ratio (OR)/risk ratio (RR) or hazard ratio (HR) and their confidence intervals (CIs) were computed using STATA 12.0 software. Q test and I2 were conducted to explore heterogeneities between studies. The present meta-analysis showed that metformin use was associated with decreased risk and lower all-cause mortality of CRC in diabetes mellitus (DM) with random-effects models (risk: OR/RR = 0.71, 95% CI, 0.64–0.80, I2 = 89.3%, P < 0.001; all-cause mortality: HR = 0.72, 95% CI, 0.62–0.83, I2 = 60.1%, P = 0.014). In addition, the study showed that metformin use was associated with a lower CRC-specific mortality in DM in cohort studies with a fixed-effects model (HR = 0.80, 95% CI, 0.70–0.92, I2 = 34.7%, P = 0.190). Overall, in this meta-analysis, we found that metformin may be a protective factor for CRC risk and prognosis in patients with DM. Further well-designed, large-scale clinical studies are needed to evaluate the accuracy of our findings and more preclinical experiments are needed to reveal the underlying mechanism of metformin.