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

O'Connor L, Bailey-Whyte M, Bhattacharya M, Butera G, Hardell KNL, Seidenberg AB, Castle PE, Loomans-Kropp HA

Journal of the National Cancer Institute, 2024

68 citations

Abstract

BACKGROUND: Metformin is among the most widely used antidiabetics medications because of its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may reduce cancer risk.

METHODS: We conducted a comprehensive systematic review and meta-analysis to investigate the association between metformin use and cancer risk, with evaluation by specific cancer type when possible. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from inception through March 7, 2023, with metformin use categorized as "ever" or "yes" and a cancer diagnosis as the outcome. Article quality was evaluated using National Heart, Lung, and Blood Institute guidelines, and publication bias was evaluated using the Egger test, Begg test, and funnel plots. Pooled relative risk (RR) estimates were calculated using random-effects models, and sensitivity analysis was completed through leave-one-out cross-validation.

RESULTS: We included 166 studies with cancer incidence information in the meta-analysis. Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93). Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer…

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