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, Zhunan, Taiwan.
Gynecol Oncol. 2015 Jul;138(1):147-53. doi: 10.1016/j.ygyno.2015.03.059. Epub 2015 Apr 22.
To evaluate metformin effects on endometrial cancer risk in Chinese female patients with type 2 diabetes mellitus (T2DM) in Taiwan.
This is a retrospective cohort analysis using the National Health Insurance database of Taiwan. Female patients with newly diagnosed T2DM and without endometrial cancer in 1998-2002 were followed to end of 2009 (n=478,921). Among them, 285,916 were never-users and 193,005 were ever-users of metformin. A time-dependent approach was used to calculate endometrial cancer incidence and estimate hazard ratios by 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.
During follow-up, 728 metformin ever-users and 2157 never-users developed endometrial cancer, representing an incidence of 60.00 and 121.69 per 100,000 person-years, respectively. The overall hazard ratio (95% confidence intervals) for ever- versus never-users after adjustment for propensity score (PS) was 0.675 (0.614-0.742). The PS-adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.089 (0.966-1.228), 0.707 (0.616-0.812) and 0.313 (0.262-0.374), respectively (P-trend<0.0001); and 1.062 (0.942-1.197), 0.620 (0.538-0.715) and 0.376 (0.317-0.447), respectively (P-trend<0.0001), for cumulative dose of metformin. The dose-response relationship was demonstrated in various models and an overall reduced risk was consistently supported by sensitivity analyses.
The use of metformin in women with T2DM was associated with an overall significantly lower risk of endometrial cancer with dose-response relationship.
评估二甲双胍对台湾地区中国女性2型糖尿病（T2DM）患者子宫内膜癌风险的影响。
这是一项利用台湾地区国民健康保险数据库进行的回顾性队列分析。对1998年至2002年新诊断为T2DM且无子宫内膜癌的女性患者进行随访至2009年底（n = 478,921）。其中，285,916例从未使用过二甲双胍，193,005例曾经使用过二甲双胍。采用时间依赖性方法计算子宫内膜癌发病率，并通过Cox回归估计曾经使用者、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）的风险比。在各个亚组中进行了敏感性分析。
随访期间，728例曾经使用二甲双胍的患者和2157例从未使用过二甲双胍的患者发生了子宫内膜癌，发病率分别为每10万人年60.00例和121.69例。在调整倾向评分（PS）后，曾经使用者与从未使用者的总体风险比（95%置信区间）为0.675（0.614 - 0.742）。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1.089（0.966 - 1.228）、0.707（0.616 - 0.812）和0.313（0.262 - 0.374）（P趋势<0.0001）；二甲双胍累积剂量的PS调整后风险比分别为1.062（0.942 - 1.197）、0.620（0.538 - 0.715）和0.376（o.317 - 0.447）（P趋势<0.0001）。在各种模型中均显示出剂量反应关系，敏感性分析一致支持总体风险降低。
T2DM女性使用二甲双胍与子宫内膜癌总体风险显著降低相关，且存在剂量反应关系。
