真实世界临床实践中 SGLT2 抑制剂与其他降血糖药物对肾脏结局的影响：日本慢性肾脏病数据库。
Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database.
机构信息
Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.
Center for Novel and Exploratory Clinical Trials, Yokohama City University, Kanagawa, Japan
出版信息
Diabetes Care. 2021 Nov;44(11):2542-2551. doi: 10.2337/dc21-1081. Epub 2021 Sep 30.
OBJECTIVE
Randomized controlled trials have shown kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown.
RESEARCH DESIGN AND METHODS
Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease.
RESULTS
At baseline, mean age at initiation of the SGLT2 inhibitor ( = 1,033) or other glucose-lowering drug ( = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m, and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26-0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors ( ≥ 0.35).
CONCLUSIONS
The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.
目的
随机对照试验已经显示钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂具有肾脏保护作用，临床实践数据库也表明这些作用可以转化为临床实践。然而，对于 2 型糖尿病（T2DM）和慢性肾脏病（CKD）患者，SGLT2 抑制剂治疗的长期疗效，以及蛋白尿的存在与否以及 SGLT2 抑制剂起始前估计肾小球滤过率（eGFR）下降的速度是否会改变治疗效果尚不清楚。
研究设计和方法
利用日本慢性肾脏病数据库（J-CKD-DB），这是一个全国性的多中心 CKD 登记处，我们开发了 SGLT2 抑制剂起始的倾向评分，并进行了 1:1 匹配，匹配对象为起始使用其他降糖药物的患者。主要结局包括 eGFR 下降率，次要结局包括 eGFR 下降 50%或终末期肾病的复合结局。
结果
在基线时，SGLT2 抑制剂（n=1033）或其他降糖药物（n=1033）起始时的平均年龄为 64.4 岁，平均 eGFR 为 68.1 mL/min/1.73 m，纳入患者中有 578 例（28.0%）存在蛋白尿。在随访期间，SGLT2 抑制剂的起始与 eGFR 下降减少相关（SGLT2 抑制剂与其他药物相比斜率差异为 0.75 mL/min/1.73 m/年[0.51 至 1.00]）。在平均 24 个月的随访期间，发生了 103 例复合肾脏结局：SGLT2 抑制剂组发生 30 例（每 1000 患者-年 14 例事件），其他药物组发生 73 例（每 1000 患者-年 36 例事件）（风险比 0.40，95%CI 0.26-0.61）。在临床试验中观察到的 SGLT2 抑制剂对肾功能的益处转化为临床实践中接受治疗的患者，并且没有证据表明这些益处会受到基础肾功能下降速度或蛋白尿存在的影响。
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