Jiang Guozhi, Luk Andrea O, Yang Xilin, Wang Ying, Tam Claudia H T, Lau Siu Him, Ozaki Risa, Kong Alice P S, Tong Peter C, Chow Chun Chung, Chan Juliana C N, So Wing Yee, Ma Ronald C W
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
Diabetes Res Clin Pract. 2016 Feb;112:57-64. doi: 10.1016/j.diabres.2015.11.003. Epub 2015 Nov 23.
To assess the development of treatment failure in Chinese patients with type 2 diabetes mellitus (T2DM) initiated on metformin or sulphonylurea (SU) monotherapy, with consideration of various potential sources of biases.
A 1:1-matched new metformin and SU user cohort on immortal time and mean propensity score after multiple imputation was selected from a cohort of 5889 Chinese patients with T2DM. Treatment failure was defined as progression to (i) combination oral anti-hyperglycemia drug therapy, (ii) insulin use, or (iii) a treatment haemoglobin A1c (HbA1c) >7.5% (58 mmol/mol). Stratified Cox regression analysis on the matched pairs was employed to examine the associations between initial monotherapy and onset of treatment failure.
Of 554 new metformin and 840 new SU users, 380 were matched. During a median follow-up duration of 3 years, 173 (45.6%) metformin users and 220 (57.9%) SU users experienced treatment failure (annual failure rates of 15% and 19%, respectively). The median time from monotherapy starting to treatment failure was 3.0 [inter-quartile range (IQR): 1.8-5.4] years for metformin users, versus 1.8 (IQR: 0.9-4.1) years for SU users (p<0.001). Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p<0.001). Consistent results were found in analyses based on traditional adjustment schemes with or without imputation.
By systematically incorporating new-user design, multiple imputation and matching methods, we found that Chinese patients with T2DM initiated on metformin monotherapy were associated with a significant delay in the onset of treatment failure compared to SU monotherapy.
评估起始使用二甲双胍或磺脲类药物(SU)单药治疗的中国2型糖尿病(T2DM)患者治疗失败的发生情况,并考虑各种潜在的偏倚来源。
从5889例中国T2DM患者队列中,选取1:1匹配的新使用二甲双胍和SU的患者队列,采用多重填补后的不朽时间和平均倾向评分进行匹配。治疗失败定义为进展至(i)联合口服降糖药物治疗,(ii)使用胰岛素,或(iii)治疗时糖化血红蛋白(HbA1c)>7.5%(58 mmol/mol)。采用配对分层Cox回归分析来检验初始单药治疗与治疗失败发生之间的关联。
554例新使用二甲双胍的患者和840例新使用SU的患者中,380例进行了匹配。在中位随访3年期间,173例(45.6%)二甲双胍使用者和220例(57.9%)SU使用者出现治疗失败(年失败率分别为15%和19%)。二甲双胍使用者从单药治疗开始至治疗失败的中位时间为3.0[四分位间距(IQR):1.8 - 5.4]年,而SU使用者为1.8(IQR:0.9 - 4.1)年(p<0.001)。分层Cox回归分析显示,二甲双胍使用者治疗失败风险显著更低(HR[95%CI],0.62[0.47 - 0.81];p<0.)。在基于传统调整方案(有或无填补)的分析中发现了一致的结果。
通过系统纳入新使用者设计、多重填补和匹配方法,我们发现与SU单药治疗相比,起始二甲双胍单药治疗的中国T2DM患者治疗失败的发生显著延迟。