Yang Qing, Lang Yanlin, Yang Wenjie, Yang Fenghao, Yang Jia, Wu Yucheng, Xiao Xiang, Qin Chunmei, Zou Yutong, Zhao Yuancheng, Kang Deying, Liu Fang
Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China; Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, China.
Division of Project Design and Statistics, West China Hospital of Sichuan University, Chengdu, China.
Diabetes Res Clin Pract. 2023 Apr;198:110592. doi: 10.1016/j.diabres.2023.110592. Epub 2023 Feb 25.
AIM: To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601). RESULTS: This network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61-0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06-1.62). Then MRAs (RR 0.77, 95%CI 0.68-0.88; MD 1.31, 95%CI 0.89-1.74), GLP-1RAs (RR 0.78, 95%CI 0.62-0.97; MD 0.75, 95%CI 0.46-1.05), and ERAs (RR 0.75, 95%CI 0.57-0.99; MD 0.7, 95%CI 0.3-1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57-0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55-0.97) and MRAs (RR 0.79, 95%CI 0.67-0.92). SGLT-2Is (RR 0.8, 95%CI 0.71-0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6-0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05-1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86-2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65-0.93) were in contrast. CONCLUSIONS: SGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.
目的：评估有前景的肾脏保护药物，包括钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2Is）、胰高血糖素样肽-1受体激动剂（GLP-1RAs）、二肽基肽酶IV抑制剂（DPP-4Is）、醛固酮受体激动剂（MRAs）、内皮素受体拮抗剂（ERAs）、己酮可可碱（PTF）和吡非尼酮（PFD），对2型糖尿病（T2DM）和慢性肾脏病（CKD）患者心血管和肾脏结局的比较疗效及安全性。 方法：检索PubMed、Embase和Cochrane图书馆自建库至2022年8月12日的文献。我们使用贝叶斯模型进行网状meta分析，并在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42022343601）进行了注册。 结果：该网状meta分析共识别出2589篇文献，纳入27项符合条件的试验，共50237例患者。以下所有结果的质量均为中到高质量。对于肾脏结局，SGLT-2Is在降低复合肾脏事件（风险比[RR]0.69，95%置信区间[CI]0.61 - 0.79）和减缓估算肾小球滤过率（eGFR）斜率（平均差[MD]1.34，95%CI 1.06 - 1.62）方面最为有效。其次是MRAs（RR 0.77，95%CI 0.68 - 0.88；MD 1.31，95%CI 0.89 - 1.74）、GLP-1RAs（RR 0.78，95%CI 0.62 - 0.97；MD 0.75，95%CI 0.46 - 1.05）和ERAs（RR 0.75，95%CI 0.57 - 0.99；MD 0.7，95%CI 0.3 - 1.1）。对于心血管结局，SGLT-2抑制剂在降低心力衰竭住院风险方面也是最佳药物之一（RR 0.67，95%CI 0.57 - 0.78），其次是GLP-1RAs（RR 0.73，95%CI 0.55 - 0.97）和MRAs（RR 0.79，95%CI 0.67 - 0.92）。SGLT-2Is（RR 0.8，95%CI 0.71 - 0.89）和GLP-1RAs（RR 0.72，95%CI 0.6 - 0.86）在降低主要不良心血管事件风险方面效果相当。MRAs可能与因不良事件导致的停药增加有关（RR 1.21，95%CI 1.05 - 1.38）。对于高钾血症结局，MRAs（RR 2.08，95%CI 1.86 - 2.33）与高钾血症风险相关，而SGLT-2Is则相反（RR 0.78，95%CI 0.65 - 0.93）。 结论：SGLT-2Is可显著降低T2DM和CKD患者的肾脏和心血管风险，其次是GLP-1RAs和MRAs。SGLT-2Is与MRAs联合使用可能是一种推荐的治疗方案，可最大程度地保护肾脏和心血管，同时降低T2DM和CKD患者高钾血症的风险。
Cochrane Database Syst Rev. 2018-9-24
Front Pharmacol. 2025-4-24
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