Association of metformin use and cancer incidence: a systematic review and meta-analysis

Abstract Background Metformin is among the most used anti-diabetic medications, due to its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may also reduce cancer risk. Methods We conducted a comprehensive systematic review and meta-analysis investigating the association between metformin use and cancer risk, with evaluation by specific cancer type when able. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane, Web of Science, and Scopus from inception through March 7, 2023. Metformin use categorized as ‘ever’ or ‘yes’, with cancer diagnosis as the outcome. Paper quality was evaluated using National Heart, Lung, and Blood Institute (NIH) guidelines and publication bias evaluated using Egger’s test and Begg’s test and funnel plot. Pooled RR estimates were calculated using random effects models and sensitivity analysis completed through leave-one-out cross-validation. Results One hundred and sixty-six studies with cancer incidence information were included in the meta-analysis. Reduced risk for overall cancer was observed in case-control (RR, 0.55; 95% CI, 0.30-0.80) and prospective cohort (RR, 0.65; 95% CI, 0.37-0.93) studies. Metformin use was associated with reduced gastrointestinal (RR, 0.79; 95%CI, 0.73-0.85), urologic (RR, 0.88; 95%CI, 0.78-0.99), and hematologic (RR, 0.87; 95%CI, 0.75-0.99) cancer risk. Significant publication bias was observed within the studies (Egger’s p < .001). Conclusions Metformin may be associated with a decreased risk for many cancer types, but high heterogeneity and risk for publication bias limit confidence in these results. Additional studies in non-diabetic populations are needed to better understand the utility of metformin in cancer prevention.