Metformin use and the risk of incident breast cancer: a systematic review and meta-analysis accounting for time-related biases, and why imeglimin cannot yet be evaluated

Metformin use is not associated with incident breast cancer in observational studies that addressed time-related biases, with a pooled RR of 1.00 (95% CI 0.94–1.08).

• Why it matters: Prior observational evidence linking metformin to lower breast cancer risk may be distorted by immortal time and time-window bias, leaving uncertainty about whether any true association exists.
• What they did: The authors pooled 12 independent cohort and case-control studies across 15 source populations using a DerSimonian-Laird random-effects model, classifying studies by new-user design, time-varying exposure, or target trial emulation.
• The result: In nine bias-addressing studies, the RR was 1.00 (0.94–1.08; I-squared = 0%), while studies not addressing bias showed RR 0.69 (0.56–0.84); imeglimin meta-analysis was not possible because no clinical cancer outcomes were reported.

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