Effect of Finerenone on CKD Outcomes in Type 2 Diabetes

Background: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) remain at risk of CKD progression despite guideline-directed therapies. Mineralocorticoid receptor (MR) overactivation may drive CKD progression through inflammatory and fibrotic processes. Finerenone, a novel, nonsteroidal MR antagonist, reduces albuminuria independent of hemodynamic effects. We assessed the long-term efficacy and safety of finerenone in slowing CKD progression in patients with CKD and T2D. Methods: This global, phase 3, double-blind study randomized 5734 patients from 48 countries (1:1) to oral finerenone or placebo. Patients with T2D, urine albuminto-creatinine ratio 30-5000 mg/g and estimated glomerular filtration rate (eGFR) 25-<75 mL/min/1.73 m2, treated with optimized renin-angiotensin system blockade, were included. The primary outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline or renal death. The key secondary outcome was time to cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke or heart failure hospitalization. (NCT02540993) Results: Mean patient age was 65.6 years; 70.2% were male. At baseline, mean eGFR was 44.3 mL/min/1.73 m2 and median UACR 852 mg/g. The primary outcome occurred in 504/2833 (17.8%) and 600/2841 (21.1%) patients treated with finerenone and placebo, respectively (hazard ratio [HR]=0.82; 95% confidence interval [CI] 0.73-0.93; p=0.0014). The prespecified secondary outcome was also reduced with finerenone (13.0%) vs placebo (14.8%; HR=0.86; 95% CI 0.75-0.99, p=0.0339). Overall treatment-emergent adverse events were balanced between groups. The incidence of hyperkalemia-related treatment discontinuation was higher with finerenone than placebo (2.3% and 0.9%, respectively). Conclusions: Finerenone significantly reduced kidney and CV outcomes in patients with T2D and advanced CKD and was well tolerated. While the primary adverse event was hyperkalemia, it only necessitated treatment discontinuation in 2.3% of patients compared to 0.9% in placebo. These data support the use of finerenone to slow CKD progression and reduce CV risk in patients with CKD and T2D. Funding: Commercial Support - Bayer AG