东京大学Masaomi Nangaku团队近日研究了芬尼酮联合恩格列净治疗慢性肾病和2型糖尿病的疗效与安全性。相关论文发表在2025年6月5日出版的《新英格兰医学杂志》上。

有限的证据支持在慢性肾病和2型糖尿病患者中同时开始使用钠-葡萄糖共转运蛋白-2抑制剂和非甾体矿物皮质激素受体拮抗剂芬烯酮。

研究组随机分配患有慢性肾病（估计肾小球滤过率[eGFR]，每分钟每1.73平方米体表面积30至90毫升）、蛋白尿（尿白蛋白与肌酐比值为100至≤5000[白蛋白以毫克计，肌酐以克计]）和2型糖尿病的参与者，他们已经服用肾素-血管紧张素系统抑制剂。以1:1:1的比例接受每天10或20毫克剂量的芬尼酮（与恩帕列净相匹配的安慰剂），每天10毫克剂量的恩帕列净（与恩帕列净相匹配的安慰剂），或芬尼酮和恩帕列净的组合。主要结局是对数转化平均尿白蛋白与肌酐比值从基线到180天的相对变化。评估了安全性。

基线时，三组参与者的尿白蛋白与肌酐比值相似；在可获得数据的参与者中，中位值为579（四分位数范围，292至1092）（联合治疗组265人，芬尼酮组258人，恩格列净组261人）。在第180天，联合治疗的尿白蛋白与肌酐比值的降低比单独使用细芬烯酮大29%（与基线变化差异的最小二乘平均比值为0.71；95%置信区间为0.61 ~ 0.82；P<0.001），比单独使用恩格列净大32%(基线变化差异的最小二乘平均比值，0.68；95% CI, 0.59 ~ 0.79；术中,0.001)。两种药物单独或联合使用都不会导致意外的不良事件。症状性低血压、急性肾损伤和导致停药的高钾血症并不常见。< br / >

研究结果表明，在同时患有慢性肾脏疾病和2型糖尿病的患者中，与单独使用任何一种治疗相比，最初使用芬尼酮加恩格列净治疗可导致尿白蛋白与肌酐比值的更大降低。

附：英文原文

Title: Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes

Author: Rajiv Agarwal, Jennifer B. Green, Hiddo J.L. Heerspink, Johannes F.E. Mann, Janet B. McGill, Amy K. Mottl, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Meike Brinker, Robert Edfors, Na Li, Markus F. Scheerer, Charlie Scott, Masaomi Nangaku

Issue&Volume: 2025-06-05

Abstract:

BACKGROUND

Limited evidence exists to support the simultaneous initiation of sodium–glucose cotransporter-2 inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in persons with chronic kidney disease and type 2 diabetes.

METHODS

We randomly assigned participants with chronic kidney disease (estimated glomerular filtration rate [eGFR], 30 to 90 ml per minute per 1.73 m2 of body-surface area), albuminuria (a urinary albumin-to-creatinine ratio of 100 to ≤5000 [with albumin measured in milligrams and creatinine measured in grams]), and type 2 diabetes, who were already taking a renin–angiotensin system inhibitor, in a 1:1:1 ratio to receive finerenone (with empagliflozin-matching placebo) at a dose of 10 or 20 mg per day, empagliflozin at a dose of 10 mg per day (with finerenone-matching placebo), or a combination of finerenone and empagliflozin. The primary outcome was the relative change in the log-transformed mean urinary albumin-to-creatinine ratio from baseline to 180 days. Safety was assessed.

RESULTS

At baseline, the urinary albumin-to-creatinine ratio was similar among the participants in the three groups; the median value was 579 (interquartile range, 292 to 1092) among those with available data (265 in the combination-therapy group, 258 in the finerenone group, and 261 participants in the empagliflozin group). At day 180, the reduction in the urinary albumin-to-creatinine ratio with combination therapy was 29% greater than that with finerenone alone (least-squares mean ratio of the difference in the change from baseline, 0.71; 95% confidence interval [CI], 0.61 to 0.82; P<0.001) and 32% greater than that with empagliflozin alone (least-squares mean ratio of the difference in the change from baseline, 0.68; 95% CI, 0.59 to 0.79; P<0.001). Neither agent, alone or in combination, led to unexpected adverse events. Symptomatic hypotension, acute kidney injury, and hyperkalemia leading to drug discontinuation were uncommon.

CONCLUSIONS

Among persons with both chronic kidney disease and type 2 diabetes, initial therapy with finerenone plus empagliflozin led to a greater reduction in the urinary albumin-to-creatinine ratio than either treatment alone.

DOI: NJ202506050000002

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2410659