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在接受 GLP-1RA 治疗的慢性肾脏病和 2 型糖尿病患者中,非奈利酮的疗效和安全性:来自 FIDELIO-DKD 试验的亚组分析。

Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment: A subgroup analysis from the FIDELIO-DKD trial.

机构信息

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

出版信息

Diabetes Obes Metab. 2022 Jan;24(1):125-134. doi: 10.1111/dom.14558. Epub 2021 Oct 11.

Abstract

AIMS

Finerenone significantly reduced the risk of kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease and type 2 diabetes in the FIDELIO-DKD trial (NCT02540993). This exploratory subgroup analysis investigates the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on the treatment effect of finerenone.

MATERIALS AND METHODS

Patients with type 2 diabetes, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate 25-<75 ml/min per 1.73 m receiving optimized renin-angiotensin system blockade were randomized to finerenone or placebo.

RESULTS

Of the 5674 patients analysed, overall, 394 (6.9%) received GLP-1RAs at baseline. A reduction in UACR with finerenone was observed with or without baseline GLP-1RA use; ratio of least-squares means 0.63 (95% confidence interval 0.56, 0.70) with GLP-1RA use and 0.69 (95% confidence interval 0.67, 0.72) without GLP-1RA use (p value for interaction .20). Finerenone also significantly reduced the primary kidney (time to kidney failure, sustained decrease in estimated glomerular filtration rate ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) versus placebo, with no clear difference because of GLP-1RA use at baseline (p value for interaction .15 and .51 respectively) or any time during the trial. The safety profile of finerenone was similar between subgroups.

CONCLUSIONS

This exploratory subgroup analysis suggests that finerenone reduces UACR in patients with or without GLP-1RA use at baseline, and the effects on kidney and CV outcomes are consistent irrespective of GLP-1RA use.

摘要

目的

在 FIDELIO-DKD 试验(NCT02540993)中,非奈利酮显著降低了慢性肾脏病和 2 型糖尿病患者的肾脏和心血管(CV)结局风险。本探索性亚组分析研究了胰高血糖素样肽-1 受体激动剂(GLP-1RA)的使用对非奈利酮治疗效果的影响。

材料和方法

本研究纳入了接受优化肾素-血管紧张素系统阻断治疗的 2 型糖尿病、尿白蛋白与肌酐比值(UACR)30-5000mg/g 和估算肾小球滤过率 25-<75ml/min/1.73m2 的患者,将其随机分配至非奈利酮或安慰剂组。

结果

在分析的 5674 例患者中,总体上有 394 例(6.9%)患者基线时使用了 GLP-1RA。非奈利酮治疗可降低 UACR,无论基线时是否使用 GLP-1RA,最小二乘均数比分别为 0.63(95%置信区间 0.56,0.70)和 0.69(95%置信区间 0.67,0.72)(交互检验 p 值.20)。与安慰剂相比,非奈利酮还显著降低了主要肾脏(肾衰竭时间、从基线开始估算肾小球滤过率持续下降≥40%或肾脏死亡)和主要次要心血管结局(心血管死亡时间、非致死性心肌梗死、非致死性卒中和因心力衰竭住院),无论基线时(交互检验 p 值.15 和.51)还是试验期间任何时候,GLP-1RA 的使用均未显示出明显差异。非奈利酮的安全性在亚组间相似。

结论

本探索性亚组分析表明,非奈利酮可降低基线时使用或不使用 GLP-1RA 的患者的 UACR,并且对肾脏和心血管结局的影响与 GLP-1RA 的使用无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b96f/9293162/d3d9d32206fd/DOM-24-125-g001.jpg

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