Impact of Baseline GLP-1 Receptor Agonist Use on Albuminuria Reduction and Safety With Simultaneous Initiation of Finerenone and Empagliflozin in Type 2 Diabetes and Chronic Kidney Disease (CONFIDENCE Trial)

Objective: The CONFIDENCE trial demonstrated additive benefits of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and a sodium-glucose cotransporter 2 (SGLT2) inhibitor compared to monotherapy in reducing urinary albumin-to-creatinine ratio (UACR). This prespecified analysis evaluated whether safety and efficacy of combination therapy varies by baseline glucagon-like peptide-1 receptor agonist (GLP-1 RA) use. Research Design and Methods: Adults with chronic kidney disease (UACR of ≥100 to <5000 mg/g; estimated glomerular filtration rate [eGFR] 30 to 90 mL/min/1.73 m²) and type 2 diabetes (glycated hemoglobin <11% [<97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin. Results: Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline (95% CI) in participants using a GLP-1 RA was −51% (−59 to −40) with combination therapy, −34% (−48 to −18) with finerenone, and −36% (−48 to −21) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were −56% (−62 to −50), −37% (−45 to −28), and −33% (−41 to −23), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed, and were more pronounced with combination therapy. Conclusion: In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well-tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA.