Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2023-10-10 DOI:10.1111/dom.15305

Nikolaos Perakakis MD, Stefan R. Bornstein MD, Andreas L. Birkenfeld MD, Andreas Linkermann MD, Münevver Demir MD, Stefan D. Anker MD, Gerasimos Filippatos MD, Bertram Pitt MD, Peter Rossing MD, Luis M. Ruilope MD, Peter Kolkhof PhD, Robert Lawatscheck MD, Charlie Scott MSc, George L. Bakris MD, FIDELIO-DKD and FIGARO-DKD investigators

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Abstract

Aim

Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis.

Materials and Methods

Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure.

Results

ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively).

Conclusions

Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications.

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finerenone对2型糖尿病、慢性肾脏疾病和肝脂肪变性和纤维化标志物改变患者的疗效：FIDELITY亚组分析。

目的：研究非诺酮对慢性肾脏病和2型糖尿病患者肝功能、心血管和肾脏综合结果的影响，并根据其肝脂肪变性、炎症和纤维化的风险进行分层。材料和方法：事后分析分层患者（N = 13 026）：脂肪变性的高风险（肝脂肪变性指数>36）；转氨酶升高[丙氨酸转氨酶（ALT）>33（男性）和>25 IU/L（雌性）]；纤维蛋白-4（FIB-4）指数得分>3.25、>2.67和>1.30。通过ALT、天冬氨酸氨基转移酶和γ-谷氨酰转移酶的变化来评估肝酶。综合肾脏结果定义为肾衰竭的发作，肾小球滤过率从基线持续下降≥57%，超过≥4 数周或肾脏死亡。复合心血管结局被定义为心血管死亡、非致命性心肌梗死、非致命中风或因心力衰竭住院。结果：ALT、天冬氨酸氨基转移酶和γ-谷氨酰转移酶水平在治疗组之间是一致的，并且始终保持稳定。无论肝脏检查是否改变，芬瑞酮都能持续降低复合肾脏结果的风险。FIB-4评分越高，复合心血管结局的发生率越高。在FIB-4亚组中，与安慰剂相比，芬瑞酮可将复合心血管结局的风险降低52%（>3.25）、39%（>2.67）和24%（>1.30）（相互作用的p值 = .01、.13和.03）。结论：芬瑞酮对慢性肾脏病和2型糖尿病患者的肝脏参数具有中性影响。在肝脏检查改变的患者中，芬瑞酮表现出强大且持续的肾脏益处，即使在FIB-4评分较高且有心血管并发症高风险的患者中也表现出显著的心血管益处。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.