Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study

Abstract

Objective: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes.

Research design and methods: Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30-5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin-angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%.

Results: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia.

Conclusions: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

Trial registration: ClinicalTrials.gov NCT02540993.

Figure 1

Cox proportional hazards model for the primary kidney outcomes and key secondary CV outcome in the FAS, with cubic B-splines of HbA_1c with three equally spaced knots stratified by region, and albuminuria and eGFR at screening. The model was fitted separately by treatment group for the primary kidney composite outcome (A) and the key secondary CV outcome (B), and with treatment interaction as a covariate for the primary kidney composite outcome (C) and the key secondary CV composite outcome (D). The reference (Ref) is mean HbA_1c (%) at baseline.

Figure 2

Composite kidney outcome (time to kidney failure, a sustained ≥40% decrease in eGFR from baseline over at least 4 weeks; or death from renal causes), secondary composite kidney outcome (time to kidney failure, a sustained ≥57% decrease in eGFR from baseline over at least 4 weeks; or death from renal causes), and CV outcomes (time to first onset of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) according to HbA_1c level at baseline (A) and insulin use at baseline (B). PY, patient-year.