非格列酮作为糖尿病肾病新型治疗方案的意义:以非格列酮第 3 期试验的心肾功能结果为重点的范围界定综述

Mustafa Arici, Bulent Altun, Mustafa Araz, Aysegul Atmaca, Tevfik Demir, Tevfik Ecder, Galip Guz, Dilek Gogas Yavuz, Alaattin Yildiz, Temel Yılmaz
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摘要

这篇由内分泌学和肾脏病学专家撰写的范围界定综述旨在探讨非格列酮(fineerenone)作为糖尿病肾病(DKD)的一种新型治疗选择的意义,其依据是非类固醇矿皮质激素受体拮抗剂(MRA)特性带来的心肾获益的生物学前景,以及非格列酮三期临床试验计划的最新证据。结合MR过度激活在心肾疾病发病机制中的作用以及当前实践模式中尚未满足的需求,对非那瑞酮在延缓DKD进展方面的重要性进行了严格审查。会议介绍了非格列酮Ⅲ期研究项目(包括 FIDELIO-DKD、FIGARO-DKD 和 FIDELITY)的疗效和安全性结果。具体而言,会议探讨了纳入估计肾小球滤过率(eGFR)保留或高白蛋白尿患者、同时使用钠-葡萄糖协同转运体-2 抑制剂(SGLT2i)或胰高血糖素样肽 1 受体激动剂(GLP-1 RA)、基线糖化血红蛋白(HbA1c)水平和胰岛素治疗、有临床意义的心衰结果以及治疗诱发的高钾血症等问题。无论基线 HbA1c 水平和伴随治疗(SGLT2i、GLP-1 RA 或胰岛素)如何,非格列酮都能减缓 DKD 的进展、减少白蛋白尿和心血管并发症的风险,并且具有良好的获益-风险特征。有关 SGLT2is 和非甾体类 MRA 在减缓或降低心肾风险方面的益处的数据不断发展,这似乎为在 DKD 的治疗中使用这些治疗支柱提供了机会,而在此之前,该领域长期缺乏治疗手段。随着人们认识到白蛋白尿是检测心肾疾病高危患者的有力标志物,这些重要的发展很可能会影响 DKD 的标准治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials
This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.
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