Sexual Dimorphism and Age Effects in CKD and Type 2 Diabetes in the CONFIDENCE Trial

INTRODUCTION: Concurrent initiation of finerenone and empagliflozin can lower albuminuria more than component therapies at Day 180 in participants with CKD and T2D. We evaluated baseline clinical characteristics and longitudinal changes in UACR across age and sex cohorts.

METHODS: In CONFIDENCE (NCT05254002), participants with T2D, CKD (eGFR 30-90 ml/min/1.73 m2), and albuminuria (UACR 100 to < 5000 mg/g) on stable doses of renin-angiotensin system inhibitors were randomized 1:1:1 to empagliflozin 10 mg/day, finerenone 10 or 20 mg/day, or both. We stratified participants by age quartiles (≤ 60 years, 61-68 years, 69-74 years, > 74 years) and sex. Outcomes included percent change in UACR from baseline over time and incidences of key adverse events.

RESULTS: Increasing age was associated with higher baseline prevalence of atherosclerotic cardiovascular disease and lower eGFR. Older age was a significant predictor of UACR reduction, with -10.2% (95% CI: -15.5, -4.6) incremental change per 10-year age increase at Day 180 (P for age effect = 0.001). Women exhibited an 18.6% (95% CI: 6.3, 29.2) greater UACR reduction at Day 180 than men (P for sex effect = 0.008). These effects were independent of treatment; there was no interaction between age (P-interaction = 0.28) or sex (P-interaction = 0.46) on combination therapy treatment effect. Safety outcomes were consistent across all demographics.

CONCLUSIONS: The UACR-lowering response of finerenone and empagliflozin scaled linearly with age (10% per decade) and sex (~20% more among women). The benefit of combination therapy was independent of age and sex.