Metformin Treatment Among Men With Diabetes and the Risk of Prostate Cancer: A Population-Based Historical Cohort Study
AMERICAN JOURNAL OF EPIDEMIOLOGY(2022)
摘要
There is conflicting evidence regarding the association between metformin treatment and prostate cancer risk in diabetic men. We investigated this association in a population-based Israeli cohort of 145,617 men aged 21-89 years with incident diabetes who were followed over the period 2002-2012. We implemented a time-dependent covariate Cox model, using weighted cumulative exposure to relate metformin history to prostate cancer risk, adjusting for use of other glucose-lowering medications, age, ethnicity, and socioeconomic status. To adjust for time-varying glucose control variables, we used inverse probability weighting of a marginal structural model. With 666,553 person-years of follow-up, 1,592 men were diagnosed with prostate cancer. Metformin exposure in the previous year was positively associated with prostate cancer risk (per defined daily dose; without adjustment for glucose control, hazard ratio (HR) = 1.53 (95% confidence interval (CI): 1.19, 1.96); with adjustment, HR = 1.42 (95% CI: 1.04, 1.94)). However, exposure during the previous 2-7 years was negatively associated with risk (without adjustment for glucose control, HR = 0.58 (95% CI: 0.37, 0.93); with adjustment, HR = 0.60 (95% CI: 0.33, 1.09)). These positive and negative associations with previous-year and earlier metformin exposure, respectively, need to be confirmed and better understood.
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关键词
glucose-lowering medications, inverse probability weighting, marginal structural models, metformin, prostate cancer, time-dependent confounding, type 2 diabetes
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