Metformin for primary prevention of colorectal neoplasms in adenoma-free populations: a systematic review and dose-response meta-analysis
Abstract
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% confidence interval, 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).
Conclusion: Metformin demonstrates effective chemoprevention against colorectal neoplasms, where the inverse association was most prominent at low-dose, long-term therapy.
Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier CRD42023394042.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,416,085 participants or records.
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