Metformin exposure in the previous year may increase the risk for prostate cancer, but exposure in the previous 2 to 7 years may lower the risk, according to a recent study.

Rachel Dankner, MD, MPH, of Sheba Medical Center in Ramat Gan, Israel, and colleagues conducted a population-based study of 145,617 men aged 21 to 90 years with newly diagnosed diabetes. Of these, 1592 were diagnosed with prostate cancer over 666,553 person-years of follow-up.

Patients exposed to metformin in the previous year had a significant 53% increased risk for a prostate cancer diagnosis per defined daily dose (DDD) before adjusting for glucose control and a significant 42% increased risk after adjusting for glucose control, Dr Dankner’s team reported in the American Journal of Epidemiology.

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Patients exposed to metformin in the previous 2 to 7 years, however, had a significant 42% decreased for prostate cancer per DDD without adjusting for glucose control and a nonsignificant 40% decreased risk after adjustment.

The authors said the positive association between metformin exposure in the previous year could be explained by reverse causation. Prostate cancer might disrupt glucose control shortly before diagnosis, prompting initiation of metformin or an increase in metformin dose. Surveillance bias also could result in reverse causation. Prior to initiating metformin or increasing the dose, clinicians could have subjected patients to more extensive examination, including PSA tests.

“If those receiving metformin in the previous year had their prostate cancer diagnosis brought forward for one of these reasons, this could lead to fewer cases being associated with the metformin given in the more distant past,” the authors explained. “Alternatively, our findings may reflect a true causal association; long-term metformin may prevent prostate cancer.”


Freedman LS, Agay N, Farmer R, Murad H, Olmer L, Dankner R. Metformin treatment among men with diabetes and the risk of prostate cancer, a population-based historical cohort study. Am J Epidemiol. Published online December 10, 2021. doi:10.1093/aje/kwab287