Effects of Vicadrostat/Empagliflozin in People With Chronic Kidney Disease: Metabolic Subgroup Analyses

Aims: In a phase 2 trial, the efficacy and safety of the highly selective aldosterone synthase inhibitor vicadrostat, alone or with empagliflozin, were investigated in people with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). Materials and Methods: Adults (n = 586) with CKD (estimated glomerular filtration rate [eGFR] 30 to < 90 mL/min/1.73 m², urine albumin-creatinine ratio [UACR] 200 to < 5000 mg/g) receiving a maximally tolerated dose of renin-angiotensin system inhibitor were randomised to receive vicadrostat (3, 10 or 20 mg) or matching placebo for 14 weeks, with or without background empagliflozin. The primary outcome, effect on albuminuria at 14 weeks, as well as systolic blood pressure (SBP) and eGFR, was assessed by T2D and obesity subgroups (body mass index [BMI]: ≥ 30 vs. < 30 kg/m²) at baseline. Results: Consistent with overall study results, the largest UACR reductions were observed in 10 and 20 mg dose groups across both subgroup analyses (adjusted mean reduction 30%–51% vs. 37%–46% in the overall study). UACR reductions were consistent in participants with and without T2D (P_INTERACTION = 0.53 and 0.40 with/without empagliflozin, respectively) and irrespective of BMI category at baseline (P_INTERACTION = 0.35 and 0.44 with/without empagliflozin, respectively). Effects of vicadrostat treatment on reductions in eGFR and SBP were also consistent across T2D and BMI subgroups. Conclusions: Effects of vicadrostat with or without empagliflozin on UACR, eGFR, and SBP were consistent irrespective of T2D and obesity status. Trial Registration: ClinicalTrials.gov identifier: NCT05182840.