依格列净治疗的慢性肾脏病合并 2 型糖尿病患者的菲列净：FIDELITY 分析。

Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis.

机构信息

Steno Diabetes Center Copenhagen, Herlev, Denmark.

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

出版信息

Diabetes Care. 2022 Dec 1;45(12):2991-2998. doi: 10.2337/dc22-0294.

DOI:10.2337/dc22-0294

PMID:35972218

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9862372/

Abstract

OBJECTIVE

Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium-glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies.

RESEARCH DESIGN AND METHODS

Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes.

RESULTS

Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79-0.96) without SGLT2i and 0.67 (95% CI 0.42-1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69-0.92) without SGLT2i and 0.42 (95% CI 0.16-1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment.

CONCLUSIONS

Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.

摘要

目的

非奈利酮可降低慢性肾脏病（CKD）和 2 型糖尿病患者的肾脏和心血管事件风险，这在 FIDELIO-DKD 和 FIGARO-DKD 这两项 3 期研究中得到了证实。在这两项研究的预设汇总分析中，评估了非奈利酮对接受钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）治疗的患者的结局影响。

研究设计和方法

纳入 UACR（尿白蛋白与肌酐比值）≥30 至 ≤5000mg/g 且估算肾小球滤过率（eGFR）≥25ml/min/1.73m2 的 2 型糖尿病患者，随机分配至非奈利酮或安慰剂组；任何时间都允许使用 SGLT2i。主要终点为心血管复合终点（心血管死亡、非致死性心肌梗死、非致死性卒中和因心力衰竭住院）和肾脏复合终点（肾衰竭、持续 eGFR 下降≥57%或肾脏死亡），以及 UACR 和 eGFR 的变化和安全性结局。

结果

在 13026 例患者中，877 例（6.7%）基线时接受 SGLT2i 治疗，1113 例（8.5%）在试验期间开始使用 SGLT2i。无 SGLT2i 治疗时，心血管复合终点的 HR 为 0.87（95%CI，0.79-0.96），有 SGLT2i 治疗时为 0.67（95%CI，0.42-1.07）。无 SGLT2i 治疗时，肾脏复合终点的 HR 为 0.80（95%CI，0.69-0.92），有 SGLT2i 治疗时为 0.42（95%CI，0.16-1.08）。基线时使用 SGLT2i 不影响非奈利酮治疗的患者的心血管或肾脏复合终点的风险降低（P 交互作用=0.46 和 0.29）；同时使用 SGLT2i 与研究治疗也不影响。