Prostate Cancer–specific Survival After Radical Prostatectomy Is Improved Among Metformin Users but Not Among Other Antidiabetic Drug Users

Abstract

<p>Background: Metformin has been linked to improved survival among diabetic prostate cancer (PCa) patients, while hyperinsulinemia and insulin usage has been related to worse prognosis. Objective: To evaluate the association of metformin and other antidiabetic drugs with PCa death and androgen deprivation therapy (ADT). Design, setting, and participants: The study cohort included 14 424 men who underwent radical prostatectomy in Finland during 1995–2013. Cases were identified, and clinical data were collected from patient files and national registries using personal identification numbers. Intervention: Information on the use of each antidiabetic drug during 1995–2014 was collected from prescription registry of the Social Insurance Institution of Finland. Outcome measurements and statistical analysis: The risks of PCa death and initiation of ADT were analyzed by antidiabetic drug use with the Cox regression method. Each antidiabetic drug group was analyzed separately to model simultaneous usage. Pre- and postdiagnostic uses were analyzed separately. Results and limitations: Prediagnostic use of antidiabetic drugs in general had no association with the risk of PCa death. Prediagnostic use of metformin was related to a reduced risk of ADT initiation (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59–0.96), while high-dose insulin users had an increased risk. Overall, antidiabetic drug use after PCa diagnosis was associated with an elevated risk of PCa death. Only postdiagnostic metformin use was associated with reduced risks of PCa death (HR 0.47, 95% CI 0.30–0.76) and ADT initiation compared with nonusers. Study limitations are missing information on glycemic control, smoking, living or exercise habits, prostate-specific antigen, and Gleason score. Conclusions: Among surgically treated PCa patients, use of metformin was associated with improved disease-specific survival, while insulin and insulin secretagogues were associated with poor survival. Metformin might be a favorable diabetes treatment among men with PCa. Patient summary: In this Finnish nationwide study, we found that the risks of prostate cancer death and cancer progression are lowered among metformin users, but not among other antidiabetic drug users. Metformin might be a favorable treatment choice for diabetes in men with prostate cancer.</p>