Tseng Chin-Hsiao
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan.
Eur J Cancer. 2014 Nov;50(16):2831-7. doi: 10.1016/j.ejca.2014.08.007. Epub 2014 Sep 5.
Whether metformin therapy affects incident prostate cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated.
The National Health Insurance reimbursement database of Taiwanese male patients with new-onset T2DM between 1998 and 2002 and aged ⩾40years (n=395,481) were retrieved to follow up prostate cancer incidence until the end of 2009. Metformin was treated as a time-dependent variable. Of the patients studied, 209,269 were never-users and 186,212 were ever-users. A time-dependent approach was used to calculate prostate cancer incidence and estimate hazard ratios using Cox regression for ever-users, never-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). Sensitivity analyses were conducted in various subgroups, using time-dependent and non-time-dependent approaches.
During the follow-up, 2776 metformin ever-users and 9642 never-users developed prostate cancer, representing an incidence of 239.42 and 737.10 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) after adjustment for propensity score (PS) for ever- versus never-users was 0.467 (0.446-0.488). The PS-adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 0.741 (0.698-0.786), 0.474 (0.441-0.508) and 0.231 (0.212-0.253), respectively (P-trend<0.001); and were 0.742 (0.700-0.786), 0.436 (0.406-0.468) and 0.228 (0.208-0.251) for the respective cumulative dose (P-trend<0.001). Sensitivity analyses consistently supported a protective effect of metformin on incident prostate cancer.
Metformin use is associated with a decreased risk of incident prostate cancer in Taiwanese male patients with T2DM.
二甲双胍治疗是否会影响亚洲2型糖尿病（T2DM）患者发生前列腺癌的风险尚未得到研究。
检索1998年至2002年间年龄≥40岁的台湾男性新发T2DM患者的国民健康保险报销数据库（n = 395,481），随访至2009年底的前列腺癌发病率。二甲双胍被视为一个随时间变化的变量。在研究的患者中，209,269例从未使用过二甲双胍，186,212例曾经使用过。采用随时间变化的方法计算前列腺癌发病率，并使用Cox回归对曾经使用者、从未使用者以及二甲双胍暴露亚组（累积持续时间和累积剂量的三分位数）估计风险比。使用随时间变化和非随时间变化的方法在各个亚组中进行敏感性分析。
在随访期间，2776例曾经使用二甲双胍的患者和9642例从未使用过的患者发生了前列腺癌，发病率分别为每10万人年239.42例和737.10例。在对倾向评分（PS）进行调整后，曾经使用者与从未使用者相比的风险比（95%置信区间）为0.467（0.446 - 0.488）。二甲双胍治疗累积持续时间的第一、第二和第三三分位数的PS调整后风险比分别为0.741（0.698 - 0.786）、0.474（0.441 - 0.508）和0.231（0.212 - 0.253）（P趋势<0.001）；累积剂量的相应风险比分别为0.742（0.700 - 0.786）、0.436（0.406 - 0.468）和0.228（0.208 - 0.251）（P趋势<0.001）。敏感性分析一致支持二甲双胍对前列腺癌发病的保护作用。
在台湾男性T2DM患者中，使用二甲双胍与前列腺癌发病风险降低相关。
