ESC Congress 2026 Abstract · Oct 26, 2026
Simultaneous versus sequential initiation of CKM therapies: an indirect comparison of CONFIDENCE and FIDELITY
By Ostrominski J, Vaduganathan M, Claggett BL et al.
Background: Clinical practice guidelines for persons with chronic kidney disease (CKD) and type 2 diabetes (T2D) recommend the combined use of the non-steroidal mineralocorticoid receptor antagonist finerenone and sodium-glucose co-transporter-2 inhibitors (SGLT2i), but there is uncertainty about the optimal timing of initiation of these therapies. Purpose: To compare the safety and efficacy of sequential versus simultaneous initiation strategies with finerenone and SGLT2i. Methods: In this individual-level pooled analysis of three phase 3 trials that enrolled persons with CKD and T2D, we compared a “sequential initiation” strategy (starting nsMRA among individuals stably on background SGLT2i) with a “simultaneous initiation” strategy (starting nsMRA and SGLT2i concurrently). The “sequential initiation” strategy was tested among 873 participants who were already on SGLT2i at baseline in 2 placebo-controlled phase 3 trials of finerenone: FIGARO-DKD (n=615) and FIDELIO-DKD (n=258). The “simultaneous initiation” strategy was tested among 526 participants in the CONFIDENCE trial which directly randomized participants to the SGLT2i empagliflozin and finerenone versus empagliflozin alone. We examined effects of finerenone on markers of efficacy (change in urine albumin-to-creatinine ratio [UACR]) and safety, restricted to 180 days to allow comparability across trials. Results: Between baseline and 14 days, the simultaneous initiation strategy was associated with a 37% reduction in UACR (ratio of geometric mean change, 0.63; 95% CI, 0.58 to 0.69), which was comparable to the reduction in UACR achieved between baseline and 120 days with the sequential strategy (ratio of geometric mean change, 0.60; 95% CI, 0.56 to 0.65). Finerenone resulted in a similar increase in serum potassium levels by day 30 with the sequential strategy (mean change, +0.16 mmol/L; 95% CI, +0.12 to +0.21 mmol/L) and simultaneous strategy (+0.22 mmol/L). Finerenone led to a similar eGFR change from baseline at 30 days with the sequential strategy (mean difference, -2.7 mL/min/1.73 m2; 95% CI, -3.8 to -1.6 mL/min/1.73 m2) and simultaneous strategy (mean difference, -1.8 mL/min/1.73 m2; 95% CI, -3.3 to -0.3 mL/min/1.73 m2). Reductions in systolic blood pressure by day 30 were comparable between the sequential (mean difference, -3.5 mm Hg; 95% CI, -5.1, -2.0 mm Hg) and simultaneous (-3.7 mmHg) strategies. Rates of hyperkalemia were higher with finerenone, but serious adverse events were infrequent, irrespective of strategy (Table). Conclusion: These findings suggest simultaneous initiation of finerenone and an SGLT2i may achieve more rapid improvement in albuminuria, and with similar safety, compared with sequential initiation.