Abstract

Metformin is associated with lower risks of developing prostate cancer (PCa), but its association with mortality in PCa is unclear. This study examined the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with PCa. Diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥6 months of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. Included patients were followed up until September 2021. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. Inverse probability treatment weighting was used to balance covariates. 1971 patients (1284 metformin users and 687 non-users; mean age 76.2±7.8 years) were studied. Over a mean follow-up of 4.1±3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio (wHR) 0.49 [95% confidence interval 0.39-0.61], p<0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p<0.001), independent of diabetic control or status of chronic kidney disease. Such associations appeared stronger in patients without androgen receptor antagonist or chemotherapy use (Table).Table: 1416PWeighted comparisons of outcomes by metformin usage with subgroups for androgen receptor antagonist or chemotherapy usage. Weighted hazard ratios (wHR) [95% confidence interval (CI)] were referenced against metformin non-usersAll patientsNever received androgen receptor antagonist or chemotherapy (N=1096)Received androgen receptor antagonist or chemotherapy (N=875)p value for interactionwHR [95% CI]p valuewHR [95% CI]p valuewHR [95% CI]p valueProstate cancer-related mortality0.49 [0.39, 0.61]<0.0010.38 [0.27, 0.52]<0.0010.59 [0.43, 0.81]0.0010.017All-cause mortality0.53 [0.46, 0.61]<0.0010.48 [0.40, 0.57]<0.0010.60 [0.48, 0.75]<0.0010.048 Open table in a new tab Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa. Its role as adjuvant therapy for PCa warrants further study.

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