FINERENONE IN CHRONIC KIDNEY DISEASE AND TYPE 1 DIABETES

Type 1 diabetes (T1D) is currently estimated to affect 9.5 million people globally, and approximately 30% of these people are expected to have chronic kidney disease (CKD). Although innovation in therapies to treat CKD in patients with type 2 diabetes (T2D) has advanced in recent years, the treatment of CKD in those with T1D remains an area of urgent unmet need due to high residual risk. The nonsteroidal mineralocorticoid receptor antagonist finerenone has demonstrated reductions in the risk of major clinical kidney and cardiovascular outcomes in patients with CKD and T2D. Reduction in urine albumin-to-creatinine ratio (UACR) explained up to 87% of the benefit of finerenone on the risk of a composite kidney outcome defined as time to kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥40% over at least 4 weeks or kidney-related death. The FINE-ONE trial (NCT05901831) assessed the efficacy and safety of finerenone in patients with CKD and T1D using change in UACR as a bridging biomarker to translate evidence of the long-term kidney benefits of finerenone from T2D to T1D.

FINE-ONE was a global, phase 3, double-blind trial evaluating finerenone in patients with CKD (UACR ≥200–<5000 mg/g; eGFR ≥25–<90 mL/min/1.73 m2), T1D, glycated hemoglobin (HbA1c) <10%, and serum potassium concentration ([K+]) ≤4.8 mmol/L. Patients receiving stable renin–angiotensin system therapy were randomized 1:1 to finerenone (10 or 20 mg once daily) or placebo. The primary efficacy outcome was change in UACR from baseline over 6 months. Safety outcomes included the proportion of participants who experienced treatment-emergent adverse events (AEs) and hyperkalemia.

A total of 242 patients were randomized to finerenone (n=120) and placebo (n=122). Median (Q1–Q3) UACR values at baseline were 575 (316–1225) mg/g in the finerenone group and 506 (288–1182) in the placebo group. Over 6 months, the least-squares geometric mean treatment ratio to baseline in UACR was 0.66 (95% CI 0.60–0.73) with finerenone vs 0.88 (95% CI 0.79–0.98) with placebo (least-squares geometric mean finerenone/placebo ratio, 0.75; 95% CI 0.65–0.87; p=0.0001). UACR reductions were not modified by baseline UACR, eGFR, systolic blood pressure, or serum [K+] levels (pinteraction>0.2; all analyses). At Month 1, eGFR declined by −2.78 (95% CI −4.15 to −1.40) mL/min/1.73 m2 (returning toward baseline during washout) and by −0.78 (95% CI −2.22 to 0.66) mL/min/1.73 m2 with placebo (difference −1.99 (95% CI −3.97 to −0.01); p=0.049). AEs were consistent with the established safety profile for finerenone. Hyperkalemia was more common with finerenone compared with placebo (n=12 [10.1%] vs n=4 [3.3%]); however, discontinuations (n=2 [1.7%] vs n=0) and hospitalizations (n=2 [1.7%] vs n=0) were uncommon. AE incidence was generally not modified by the finerenone-associated change in eGFR at Month 1.

In FINE-ONE, finerenone reduced UACR compared with placebo over 6 months of treatment and had a tolerable safety profile in patients with CKD and T1D. These results imply that finerenone may afford long-term benefits in patients with T1D and CKD.

Part of these data were previously presented at the American Society of Nephrology 2025 congress.