Kidney Compass: CONFIDENCE Trial at ERA 2025, with Rajiv Agarwal, MD, MS

Welcome to Kidney Compass: Navigating Clinical Trials!

Simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with chronic kidney disease (CKD) and type 2 diabetes was well-tolerated and resulted in significantly greater reductions in urinary albumin-to-creatinine ratio (UACR) than either agent alone, according to results from the CONFIDENCE trial presented at the 62nd European Renal Association (ERA 2025) Congress.

Led by Rajiv Agarwal, MD, Professor Emeritus at Indiana University School of Medicine, the phase 2 trial enrolled 800 patients with CKD and type 2 diabetes who were randomized in a 1:1:1 ratio to receive empagliflozin monotherapy, finerenone monotherapy, or combination therapy with simultaneous initiation. Finerenone dosing was stratified by estimated glomerular filtration rate (eGFR): 20 mg daily for eGFR ≥60 mL/min/1.73 m² and 10 mg daily for eGFR <60 mL/min/1.73 m².

The primary endpoint was the relative change in mean UACR from baseline to day 180.

Results suggested combination therapy achieved a 52% reduction in UACR from baseline, corresponding to a least-squares mean ratio of 0.48 (95% CI, 0.44 to 0.54). Compared with monotherapy, combination therapy resulted in a 29% greater reduction in UACR than finerenone alone (least squares mean ratio of difference, 0.71; 95% CI, 0.61 to 0.82; P <.001) and a 32% greater reduction than empagliflozin alone (least squares mean ratio of difference, 0.68; 95% CI, 0.59 to 0.79; P <.001).

Safety analyses indicated the combination was also well tolerated, with serious adverse events reported in 7.1% of the combination group, 6.1% in the finerenone group, and 6.4% in the empagliflozin group. Hyperkalemia led to treatment discontinuation in 1 patient per group.

During the ERA 2025 Congress, Kidney Compass host Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and the director of the Kidney Trials Unit with Royal North Shore Hospital, holds a discussion with Agarwal about the study results, but also what it means for CKD management landscape in real-world settings.

Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Agarwal include Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, and Novartis.

References:

Agarwal R, Green JB, Heerspink HJL, et al. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes. New England Journal of Medicine. Published online June 5, 2025. doi: 10.1056/nejmoa2410659