SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
This article is part of the Research TopicAdvances in the Potential Treatments of Gastrointestinal and Liver Diseases: Addressing the Public Health Burden, Volume IIView all 8 articles
Metformin for primary prevention of colorectal neoplasms in adenoma-free populations: a systematic review and dose-response meta-analysis
Provisionally accepted
- 1Suzhou Municipal Hospital, Suzhou, China
- 2Nanjing Medical University Gusu School, Suzhou, China
- 3Wuxi Huishan Geriatric Hospital, Wuxi, China
- 4Chengnan Street community health service, Suzhou, China
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Background: Metformin shows promise in preventing colorectal cancer (CRC) and its precursors, but evidence on its dose-response effect remains limited. Aim: To determine the association between metformin therapy and colorectal neoplasms in adenoma-free individuals and characterize the dose-response relationship. Methods: Adjusted effect estimates from each study were aggregated using a random-effect model. Subgroup analyses, publication bias assessment, sensitivity analyses and dose-response analyses were conducted. Results: A total of 37 eligible studies, involving 1,416,085 participants, were included. Metformin significantly reduced colorectal neoplasms risk (Hazard ratio (HR) = 0.79, 95% confidence interval (CI), 0.73–0.85, Odds ratio (OR) = 0.80, 95% CI, 0.74–0.87). Subgroup analyses demonstrated enhanced efficacy in Asian populations, younger patients (<60 years), and cohorts with ≥50% male participants. Dose-response analysis identified 331 mg/day as the optimal dose for CRC risk reduction (OR = 0.83, 95% CI, 0.76–0.91). Each additional year of use reduced CRC risk by 3% (OR = 0.97, 95% CI, 0.95– 0.99). Conclusions: Metformin demonstrates effective chemoprevention against colorectal neoplasms, where the inverse association was most prominent at low-dose, long-term therapy.
Keywords: Metformin, Colorectal neoplasm, Cancer, Adenoma, Primary Prevention
Received: 11 Jun 2025; Accepted: 05 Nov 2025.
Copyright: © 2025 Shen, Lu, Xu, Zhou, Sheng and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qiang Yu, jungle0102sz@163.com
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