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

Abstract

AimInvestigating 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 MethodsPost 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.ResultsALT, 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).ConclusionsFinerenone 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.

Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions

“…Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist that induces natriuresis with reduced hyperkalaemia compared with steroidal antagonists, potentially provides anti-inflammatory and antifibrotic effects in DKD [153]. Finerenone inhibits MR over-activation and has recently been shown to slow the progression of CKD and reduce the risk of CV events in T2D [173]. In addition, preclinical studies have demonstrated the anti-inflammatory effects of SGLT2 inhibitors empagliflozin and dapagliflozin in association with a reduction in albuminuria and renal fibrosis in DKD [174,175].…”