Initial Combination of Finerenone and Empagliflozin Achieves Greater Reduction in Albuminuria in CKD and Type 2 Diabetes.

The CONFIDENCE trial, published in The New England Journal of Medicine, evaluated the efficacy and safety of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and empagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor, in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Eligible participants had an estimated glomerular filtration rate (eGFR) between 30 and 90 mL/min/1.73 m², albuminuria (urinary albumin-to-creatinine ratio [UACR] 100–5000 mg/g), and were on maximally tolerated renin–angiotensin system inhibition.

A total of 800 participants were randomized to finerenone alone, empagliflozin alone, or the combination, for 180 days. The primary endpoint was the relative change in log-transformed mean UACR from baseline to day 180.

At baseline, median UACR was approximately 579 mg/g across groups. At day 180, UACR reduction with combination therapy was 29% greater versus finerenone alone (least-squares mean ratio [LSMR] 0.71; 95% CI, 0.61–0.82; p<0.001) and 32% greater versus empagliflozin alone (LSMR 0.68; 95% CI, 0.59–0.79; p<0.001). The proportion of patients achieving >50% UACR reduction was 54.6% with combination therapy, compared with 35.6% (finerenone) and 31.9% (empagliflozin).

Reductions were evident by day 14 and exceeded 40% by day 90. After discontinuation, UACR partially rebounded but remained below baseline in the combination and finerenone groups. Safety outcomes were comparable across groups, with low rates of treatment discontinuation due to adverse events (<5%). Hyperkalemia incidence was slightly lower with combination therapy than with finerenone alone, and acute kidney injury was rare.

Investigators highlight that early combination therapy may overcome clinical inertia and achieve more rapid renoprotection than sequential therapy. However, the study was limited by its use of a surrogate endpoint and short follow-up, precluding assessment of long-term kidney or cardiovascular outcomes.

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#CKD #Type2Diabetes #Finerenone #Empagliflozin #Nephrology