AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Combination of Finerenone with Empagliflozin According to Frailty Status Among Participants with Type 2 Diabetes and CKD in the CONFIDENCE Trial
By Chatur S, Green J, Mann J et al.
Background: The CONFIDENCE trial demonstrated additive albuminuria-lowering benefits of simultaneous initiation of SGLT2i and nsMRA among patients with T2D and CKD. Contemporary guidelines increasingly support combination therapy for T2D with persistent albuminuria on background RASi therapy. While frail patients face increased cardio-kidney risk, clinicians may be reluctant to initiate combination therapy in this vulnerable population due to concerns of tolerability, comorbidity, polypharmacy, and uncertain risk-benefit profile. Methods: The CONFIDENCE trial was a double-blind, double-dummy trial which assessed the effect of finerenone plus empagliflozin, finerenone alone, or empagliflozin alone on top of baseline RASi among patient with CKD and T2D. Frailty was assessed using a 28-item Rockwood cumulative deficit frailty index (FI) derived from medical history, vital signs, laboratory values, and medication use and categorized as: not frail (FI I≤ 0.210), more frail (FI II, 0.211-0.310), and most frail (FI III, ≥0.311). The effects of combination therapy on the relative change in UACR from baseline to day 180 and safety outcomes across baseline frailty risk categories were assessed. Results: Among 796 participants with calculable FI, the median FI was 0.27 [0.21-0.32]. Overall, 21%, 49%, and 30% were classified as not frail, more frail, and most frail, respectively. At 180 days, combination therapy significantly reduced UACR levels across all frailty risk categories (not frail: -52.7%; more frail: -55.6%; most frail: -56.9%); Figure 1. Compared with finerenone monotherapy, combination therapy resulted in similar or greater relative reductions in UACR with increasing frailty risk (P Interaction =0.002), whereas treatment effects relative to empagliflozin monotherapy remained consistent across frailty categories (P Interaction =0.67); Figure 2 . Treatment effects of combination therapy relative to either monotherapy were consistent across frailty risk categories among a range of safety endpoints including any adverse event (P Interaction =0.49), serious adverse event (P Interaction =0.59), hyperkalemia (P Interaction =0.34), early eGFR declines (>30% within 30 days) (P Interaction =0.75) and both change from baseline in systolic blood pressure (Day 14: P Interaction =0.56; Day 180: P Interaction =0.76) and eGFR (Day 14: P Interaction =0.53; Day 180: P Interaction =0.34). Conclusion: In the CONFIDENCE trial, frailty was common, affecting more than three-quarters of participants with T2D and CKD. Relative to monotherapy, combination therapy with empagliflozin and finerenone resulted in at least as much UACR lowering over a 180-day period and appeared safe and well tolerated even among participants with the greatest frailty. These findings support the efficacy and tolerability of combination therapy even among patients with the greatest frailty burden.