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)

Abstract

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 with monotherapy in reducing the 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 ≥100 to <5,000 mg/g; estimated glomerular filtration rate [eGFR] 30–90 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 in participants using a GLP-1 RA was −51% (95% CI −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. CONCLUSIONS 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.