Metformin has been postulated to have beneficial effects on prostate cancer (PC) development and survival, but the data are inconclusive. We aimed to evaluate the association between metformin use and survival outcomes in diabetic patients with PC within a large, contemporary, multicenter, international prospective contemporary cohort.
We analyzed data from RADICAL-PC (NCT0412763), a prospective cohort of newly diagnosed PC patients or patients initiating ADT for the first time. The current analysis was limited to participants with diabetes. Participants were followed for mortality data at least annually. Cox proportional hazards regression analysis was used to characterize the association between metformin use and overall survival.
Among 4489 patients, 818 (18%) had diabetes (mean age 71±7 years), of whom 611 (75%) were metformin users. Metformin users were slightly younger, less educated, more likely to be lifetime non-smokers, less likely to have metastatic disease at baseline but were more likely to have cardiovascular disease and being treated with radiotherapy. During a median follow-up of 26 (IQR 14-61) months, 46 (8%) of metformin users and 49 (35%) non-users died. After multivariable adjustment for confounders (race, education, tobacco, metastases, Gleason grade, systolic blood pressure, glomerular filtration rate and HbA1c), metformin usage was associated with a decreased risk of death (HR 0.36, 95% CI 0.21-0.61; p<0.001). Cardiovascular disease events and PC-death or new metastases were similar between metformin users and non-users.
Among diabetic patients with PC, metformin use is associated with substantially lower overall mortality. While this reduction in mortality is likely influenced by confounding factors, the observed survival advantage warrants further investigation. Specifically, longer follow-up is imperative to validate this finding and to better clarify the causes of death that drive this observation.
Canadian Cancer Society, Movember Foundation and Tolmar Pharmaceutiques Canada Inc