Abstract
INTRODUCTION: Finerenone demonstrated kidney and cardiovascular benefits in participants with chronic kidney disease (CKD) and type 2 diabetes (T2D) on optimized renin-angiotensin system (RAS) inhibition in FIDELITY, a pooled individual-level analysis of 2 clinical trials. Considering that treatment recommendations increasingly support combination therapies for CKD and T2D, this FIDELITY subanalysis assessed the efficacy and safety of finerenone versus placebo when taken with concomitant sodium-glucose cotransporter-2 inhibitor (SGLT-2i) and/or glucagon-like peptide-1 receptor agonist (GLP-1RA). METHODS: Change in urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and systolic blood pressure (SBP) over time, and treatment-emergent adverse events (TEAEs) were analyzed in subgroups by concomitant medication at baseline as follows: (i) combined SGLT-2i and GLP-1RA (n = 167), (ii) no SGLT-2i or GLP-1RA (n = 11,341), (iii) SGLT-2i only (n = 706), and (iv) GLP-1RA only (n = 776). RESULTS: Finerenone led to a greater reduction than with placebo in UACR and SBP from baseline to month 4 across all concomitant medication subgroups. At month 12, the greatest UACR reduction difference between the treatment arms was observed in the finerenone subgroup with combined SGLT-2i and GLP-1RA. Decline of eGFR from baseline was slower with finerenone than with placebo across all subgroups. The safety profile of finerenone was not modified by concomitant SGLT-2i and/or GLP-1RA use; hyperkalemia events leading to treatment discontinuation or hospitalization with finerenone were low. CONCLUSION: The concomitant use of finerenone with SGLT-2i and/or GLP-1RA demonstrated potential synergistic effects on preserving kidney function and reducing blood pressure versus placebo in people with CKD and T2D.