第二型糖尿病人使用SGLT2抑制劑與糖尿病腎病變之回溯性世代研究

A Retrospective Cohort Study of the Sodium Glucose Cotransporter 2 Inhibitors and Diabetic Kidney Disease Progression in Type 2 Diabetic Patients

蔡加睿(Jia-Ruei Tsai) ； 陳永年(Yung-Nien Chen) ； 陳榮福(Jung-Fu Chen)

《內科學誌》 34卷1期 (2023/02) Pp. 39-49

https://doi.org/10.6314/JIMT.202302_34(1).07

摘要

糖尿病腎病變（Diabetic kidney disease, DKD）在台灣是造成病人需要接受透析治療的首要病因，2019年台灣新發透析患者主診斷為糖尿病的比率高達47.9%。目前許多大型隨機分配的臨床試驗皆顯示第二型糖尿病人使用SGLT2抑制劑可以減緩病人白蛋白尿的進展，降低末期腎病變（End stage renal disease, ESRD）的發生或是腎病事件相關的死亡風險。真實世界關於糖尿病患使用SGLT2抑制劑是否可以減少腎功能惡化或末期腎病變的發生研究並不多，因此本研究回溯性調查從2015年1月1日至2021年12月31日有參加糖尿病照護網的病人，經nested case-control study，以年齡、性別和慢性共病症做配對，依有／無使用SGLT2抑制劑1:2比例納入分析，共2455位病人（分別為848位1607位）。比較腎臟試驗終點的指標，包括持續減少≧40%起始腎絲球過濾率（glomerular filtration rate,GFR）和末期腎病變（GFR<15mL/min/1.73m^2）。經校正起始糖化血色素（Glycated Hemoglobin, HbA1c）及其他影響腎臟功能的可能干擾因子，使用SGLT2抑制劑可以減緩病人慢性腎病變（chronic kidney disease, CKD）的進展，風險比（hazard ratio, HR）0.59，95%信賴區間（95%CI）0.45-0.77；依據起始腎功能的不同，GFR≧45mL/min/1.73m^2和GFR15-44mL/min/1.73m^2的病人風險比HR分別為0.66（95%CI,0.50-0.88）和0.44（95%CI,0.21-0.91）。在進展到末期腎病變的風險指標，全部研究群體HR0.20（95%CI,0.1-0.39）；GFR≧45mL/min/1.73m^2和GFR 15-44mL/min/1.73m^2的病人風險比HR分別為0.20（95%CI,0.07-0.54）和0.35（95%CI,0.13-0.96）。我們的研究發現第二型糖尿病人使用SGLT2抑制劑可以延緩病人的慢性腎病變惡化及降低末期腎病變的風險，在起始腎功能較差的病人族群（GFR 15-44mL/min/1.73m^2）使用SGLT2抑制劑改善腎功能惡化的助益更加明顯。

關鍵字

糖尿病腎病變（Diabetic kidney disease, DKD） ； 末期腎病變（End stage renal disease, ESRD） ； SGLT2抑制劑（Sodium-glucose cotransporter 2 inhibitors, SGLT2 Inhibitors）

並列摘要

Diabetic kidney disease (DKD) is the leading cause of dialysis in Taiwan. In 2019, 47.9% of incident end-stage renal disease (ESRD) patients have pre-exiting DKD. Many large randomized clinical trials have shown that the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with type 2 diabetes can reduce the risk of albuminuria, the occurrence of ESRD, or the risk of renal death. Nonetheless, real-world data for the use of SGLT2is on DKD progression and the development of ESRD remains scarce. Therefore, this study retrospectively investigated patients participated in diabetes care network from January 1, 2015 to December 31, 2021. A total of 2455 patients were enrolled; 848 were on SGLT2is. The renal outcome measures were CKD progression: ≥40% decreased from baseline glomerular filtration rate (GFR), ESRD (GFR<15 mL/min/1.73m^2). After adjusting for possible cofounders, the use of SGLT2is can reduce the progression of chronic kidney disease in patients, hazard ratio (HR) of 0.59 (95% confidence interval [95% CI],0.45-0.77). The HR for GFR≥45 mL/min/1.73m^2 and 15-44 mL/min/1.73m^2 was 0.66 (95% CI, 0.50-0.88) and 0.44 (95% CI, 0.21-0.91), respectively. From our study, the use of SGLT2is in patients with type 2 diabetes can improve the progression of chronic kidney disease (CKD) and the risk of ESRD. The benefit of SGLT2is is more pronounced in moderate to advanced CKD patients.