Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by diuretic use: A FIDELITY analysis

Aims: This post hoc analysis aimed to assess the efficacy and safety of the non-steroidal mineralocorticoid receptor antagonist finerenone by baseline diuretic use in FIDELITY, a pre-specified pooled analysis of the phase III trials FIDELIO-DKD and FIGARO-DKD.

Methods and results: Eligible patients with type 2 diabetes (T2D) and chronic kidney disease (CKD; urine albumin-to-creatinine ratio [UACR] ≥30-<300 mg/g and estimated glomerular filtration rate [eGFR] ≥25-≤90 ml/min/1.73 m², or UACR ≥300-≤5000 mg/g and eGFR ≥25 ml/min/1.73 m²) were randomized 1:1 to finerenone or placebo. Patients were analysed by baseline diuretic use (yes/no) and type of diuretic (loop or thiazide). Key efficacy outcomes included a cardiovascular composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and a kidney composite (kidney failure, sustained ≥57% decrease in eGFR, or kidney-related death). Out of 12 990 patients, 51.6% were taking diuretics at baseline (21.6% loop; 24.2% thiazide diuretics). Finerenone reduced the risk of cardiovascular and kidney composite outcomes versus placebo; diuretic use did not modify this effect on the cardiovascular (p-interaction = 0.94) or kidney outcomes (p-interaction = 0.55). Hyperkalaemia incidences were similar between finerenone subgroups irrespective of diuretic use and lower with placebo versus finerenone (with diuretics: finerenone 13.7% vs. placebo 5.7%; without diuretics: 14.3% vs. 8.3%). The incidence of hyperkalaemia leading to hospitalization or study drug discontinuation was low across treatment groups irrespective of diuretic use.

Conclusion: This analysis showed that the efficacy and safety of finerenone in patients with CKD and T2D was not modified by baseline diuretic use.