Eliciting the Impact of Metformin and Statins on Prostate Cancer Outcomes from a Real-life National Database Analysis

Several large analyses have revealed contradictory results regarding the association between prostate cancer (PC) survival and the use of statins prescribed for prevention of dyslipidaemia or atherosclerosis complications, or of metformin prescribed for type 2 diabetes (T2D). Using data collected between 2006 and 2018 in French national health databases for 521 052 men with PC and 1 827 345 men without PC, we evaluated current evidence regarding overall survival for men with PC according to statin and/or metformin use. The highest mortality was observed in PC patients exposed to both statins and metformin (hazard ratio [HR] 2.29, 95% confidence interval [CI] 2.25-2.33). However, for patients whose first PC treatment was androgen deprivation therapy, a protective effect was observed for statin alone exposure (HR 0.91, 95% CI 0.88-0.93) and combined statin and metformin exposure (HR 0.86, 95% CI 0.85-0.87), whereas men with metformin exposure alone had higher mortality (HR 1.07, 95% CI 1.03-1.11) in comparison to non-users. This protective effect of statins was not observed for PC patients treated with radical prostatectomy. The result was confirmed using causal analysis in a Bayesian network, followed by semantic elicitation using generative artificial intelligence that compiles web-based human knowledge and dedicated literature.