Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Diabetologia. 2024 Nov;67(11):2459-2470. doi: 10.1007/s00125-024-06257-7. Epub 2024 Aug 29.
AIMS/HYPOTHESIS: Although the benefits of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) are well established, the effects of these therapeutic agents in patients with advanced CKD are less certain. We hypothesised that the continued use of these drugs, even when renal function deteriorates to stage 4 CKD or worse, is safe and associated with improved cardiorenal survival.
This is a retrospective cohort study utilising data from medical records from two institutions. All patients with type 2 diabetes mellitus who were prescribed an SGLT2i between 1 January 2016 and 31 December 2021, who subsequently had eGFR <30 ml/min per 1.73 m recorded on two occasions at least 90 days apart, were identified. The date on which the eGFR first reached any level less than 30 ml/min per 1.73 m was defined as the index date. Individuals were then categorised into the SGLT2i continuation group or the discontinuation group according to the use of SGLT2i after the index date. Inverse probability of treatment weighting (IPTW) was performed to minimise confounding. Outcomes of interest included heart failure outcomes, cardiovascular outcomes, renal outcomes and safety outcomes.
According to the eligibility criteria, 337 patients in the continuation group and 358 in the discontinuation group were identified. After IPTW, continuation of SGLT2i use was associated with significantly lower risks of the composite of major adverse cardiovascular events compared with discontinuation of SGLT2i use (HR 0.65 [95% CI 0.43, 0.99]), largely driven by reduced risk of myocardial infarction during follow-up (subdistribution HR [SHR] 0.43 [95% CI 0.21, 0.89]). The incidences of an eGFR decline of 50% or more (SHR 0.58 [95% CI 0.42, 0.81]) and all-cause hospital admission (SHR 0.77 [95% CI 0.64, 0.94]) were also significantly lower in the continuation group. None of the studied safety outcomes were significantly different when comparing the two groups. Blood haemoglobin levels were significantly higher in the continuation group at the end of follow-up (114.6 g/l vs 110.4 g/l, with a difference of 4.12 g/l; p=0.047).
CONCLUSIONS/INTERPRETATION: In patients with CKD who were treated with an SGLT2i, continuation of SGLT2i use after eGFR declined to 30 ml/min per 1.73 m or less was associated with lower risks of cardiovascular and renal events compared with discontinuation of SGLT2i use. Continued use of SGLT2i throughout the course of CKD should be considered to optimise patient outcomes.
目的/假设：尽管钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）在慢性肾脏病（CKD）中的应用益处已得到充分证实，但这些治疗药物在晚期 CKD 患者中的疗效尚不确定。我们假设，即使肾功能恶化至 4 期 CKD 或更差，继续使用这些药物也是安全的，并与改善心肾生存相关。
这是一项利用来自两家机构的病历数据进行的回顾性队列研究。所有在 2016 年 1 月 1 日至 2021 年 12 月 31 日期间接受 SGLT2i 治疗的 2 型糖尿病患者，随后至少两次记录到两次相隔至少 90 天的 eGFR<30ml/min/1.73m，均被纳入研究。eGFR 首次降至<30ml/min/1.73m 的日期定义为索引日期。然后，根据索引日期后是否继续使用 SGLT2i，将患者分为 SGLT2i 继续使用组或停药组。采用逆概率治疗加权（IPTW）最小化混杂因素。主要研究终点包括心力衰竭结局、心血管结局、肾脏结局和安全性结局。
根据入选标准，继续治疗组有 337 例患者，停药组有 358 例患者。经过 IPTW 后，与停药组相比，继续使用 SGLT2i 与主要不良心血管事件复合结局的风险显著降低（HR 0.65[95%CI 0.43,0.99]），这主要归因于随访期间心肌梗死风险降低（亚分布 HR[SHR]0.43[95%CI 0.21,0.89]）。eGFR 下降 50%或更多（SHR 0.58[95%CI 0.42,0.81]）和全因住院（SHR 0.77[95%CI 0.64,0.94]）的发生率在继续治疗组也显著降低。与停药组相比，两组的安全性结局均无显著差异。在随访结束时，继续治疗组的血红蛋白水平显著升高（114.6g/L 比 110.4g/L，差异为 4.12g/L；p=0.047）。
结论/解释：在接受 SGLT2i 治疗的 CKD 患者中，与停药相比，eGFR 下降至<30ml/min/1.73m 后继续使用 SGLT2i 与心血管和肾脏事件风险降低相关。应考虑在 CKD 病程中持续使用 SGLT2i，以优化患者结局。
