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2型糖尿病合并慢性肾脏病患者中钠-葡萄糖协同转运蛋白2抑制剂的继续使用与停用及心肾结局:一项基于目标试验模拟框架的全国性队列研究

Continuation Versus Discontinuation of Sodium-Glucose Cotransporter-2 Inhibitors and Cardiorenal Outcomes Among Patients With Type 2 Diabetes and Chronic Kidney Disease: A Nationwide Cohort Study With a Target Trial Emulation Framework.

作者信息

Dong Yaa-Hui, Chang Chia-Hsuin, Wu Li-Chiu, Toh Sengwee

机构信息

Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

Clin Transl Sci. 2025 Aug;18(8):e70319. doi: 10.1111/cts.70319.

Abstract

Clinical guidelines recommend continuation of sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment when renal function deteriorates among patients with type 2 diabetes. However, the recommendation is not currently supported by research specifically designed to compare continuation versus discontinuation of SGLT2is for patients who have received the treatment for a while before experiencing renal function deterioration. Using linked Taiwanese databases with claims and clinical data and a target trial emulation framework, we conducted a nationwide cohort study to investigate the association between SGLT2i continuation and major cardiorenal outcomes after renal function declined. We identified patients with type 2 diabetes who received SGLT2is during 2016-2020, who either continued or discontinued SGLT2is within 180 days after their eGFR declined below 45 mL/min/1.73 m. The study outcomes were myocardial infarction, stroke, heart failure, acute kidney injury, and all-cause mortality. We estimated the on-treatment and intention-to-treat hazard ratios (HRs) and 95% confidence intervals (CIs) comparing SGLT2i continuation versus SGLT2i discontinuation, adjusting for baseline and time-varying covariates using inverse probability weighting. Among 11,467 eligible patients, the on-treatment HR associated with SGLT2i continuation was 0.83 (95% CI, 0.59-1.18) for myocardial infarction, 0.74 (0.56-0.95) for stroke, 0.58 (0.49-0.69) for heart failure, 0.53 (0.45-0.63) for acute kidney injury, and 0.51 (0.42-0.61) for all-cause mortality. The results did not change meaningfully in the intention-to-treat analysis or within pre-specified patient subgroups, including patients with eGFR below 30 mL/min/1.73 m or prior acute kidney injury. Our findings provide scientific evidence to support continuing SGLT2i use when renal function declines during the SGLT2i treatment course.

摘要

临床指南建议,2型糖尿病患者肾功能恶化时应继续使用钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)进行治疗。然而,目前尚无专门针对已接受一段时间SGLT2i治疗后出现肾功能恶化的患者比较继续使用与停用SGLT2i的研究来支持这一建议。利用台湾地区链接的医保理赔和临床数据库以及目标试验模拟框架,我们开展了一项全国性队列研究,以调查肾功能下降后继续使用SGLT2i与主要心肾结局之间的关联。我们纳入了2016年至2020年期间接受SGLT2i治疗的2型糖尿病患者,这些患者在估算肾小球滤过率(eGFR)降至低于45 mL/min/1.73 m²后的180天内继续或停用了SGLT2i。研究结局包括心肌梗死、中风、心力衰竭、急性肾损伤和全因死亡率。我们采用逆概率加权法对基线和随时间变化的协变量进行调整,估算了比较继续使用与停用SGLT2i的治疗中及意向性治疗风险比(HR)和95%置信区间(CI)。在11467例符合条件的患者中,继续使用SGLT2i的治疗中心肌梗死的HR为0.83(95%CI,0.59 - 1.18),中风为0.74(0.56 - 0.95),心力衰竭为0.58(0.49 - 0.69),急性肾损伤为0.53(0.45 - 0.63),全因死亡率为0.51(0.42 - 0.61)。在意向性治疗分析中或在预先设定的患者亚组(包括eGFR低于30 mL/min/1.73 m²的患者或既往有急性肾损伤的患者)中,结果没有明显变化。我们的研究结果为SGLT2i治疗过程中肾功能下降时继续使用SGLT2i提供了科学依据。

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