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J Clin Oncol 31:3069-3075.
Princess Margaret Hospital, University Health, Toronto, ON, Canada
PURPOSE: To evaluate the association between cumulative duration of metformin use after prostate cancer (PC) diagnosis and all-cause and PC-specific mortality among patients with diabetes.
PATIENTS AND METHODS: We used a population-based retrospective cohort design. Data were obtained from several Ontario health care administrative databases. Within a cohort of men older than age 66 years with incident diabetes who subsequently developed PC, we examined the effect of duration of antidiabetic medication exposure after PC diagnosis on all-cause and PC-specific mortality. Crude and adjusted hazard ratios (HRs) were calculated by using a time-varying Cox proportional hazard model to estimate effects.
RESULTS: The cohort consisted of 3,837 patients. Median age at diagnosis of PC was 75 years (interquartile range [IQR], 72 to 79 years). During a median follow-up of 4.64 years (IQR, 2.7 to 7.1 years), 1,343 (35%) died, and 291 patients (7.6%) died as a result of PC. Cumulative duration of metformin treatment after PC diagnosis was associated with a significant decreased risk of PC-specific and all-cause mortality in a dose-dependent fashion. Adjusted HR for PC-specific mortality was 0.76 (95% CI, 0.64 to 0.89) for each additional 6 months of metformin use. The association with all-cause mortality was also significant but declined over time from an HR of 0.76 in the first 6 months to 0.93 between 24 and 30 months. There was no relationship between cumulative use of other antidiabetic drugs and either outcome.
CONCLUSION: Increased cumulative duration of metformin exposure after PC diagnosis was associated with decreases in both all-cause and PC-specific mortality among diabetic men.
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