Simultaneous initiation of finerenone and empagliflozin reduces albuminuria in CKD and T2D
ERA 2025 – In the CONFIDENCE trial, combination therapy with finerenone and empagliflozin led to greater reductions in albuminuria compared with either agent alone in patients with CKD and T2D.
This summary is based on the presentation of Peter Rossing, MD, PhD (Copenhagen, Denmark), Hiddo Heerspink, PhD (Groningen, the Netherlands), Rajiv Agarwal, MD (Indianapolis, IN, USA), and Johannes Mann, MD (Munich, Germany) at the ERA Congress 2025 – The CONFIDENCE trial: Efficacy/safety of combining finerenone with empagliflozin in people with chronic kidney disease and type 2 diabetes.
Introduction and methods
For the management of patients with T2D and CKD, there are various treatment options available, such as ACEi or ARB, SGLT2 inhibitors, nonsteroidal MRAs, and GLP-1RAs. However, there is limited data on the implementation and simultaneous combination of these different treatment modalities in patients with T2D and CKD. The aim of the CONFIDENCE trial was to examine the efficacy and safety of the combination of finerenone and empagliflozin in patients with CKD and T2D.
The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint) trial was an international, double-blind multicenter phase 2 RCT in which 800 patients with T2D and CKD were randomized in a 1:1:1 ratio to finerenone (10 mg or 20 mg once daily) plus empagliflozin (10 mg once daily), finerenone (10 mg or 20 mg once daily) plus placebo or empagliflozin (10 mg once daily) plus placebo for 180 days. Randomization was stratified by urinary albumin-to-creatinine ratio (UCAR) (<850 or >850) and eGFR (<60 or ≥60). Key inclusion criteria were eGFR 30-90 mL/min/1.73 m², UCAR ≥100-<5000 mg/g, T2D with HbA1c <11%, and clinically maximum tolerated dose of ACEi/ARB for >1 month. After the treatment period, a washout period of 30 days was included to assess off-drug effects.
The primary efficacy endpoint was the relative change in the log-transformed mean UCAR from baseline to 180 days.
Main results
- The relative change in UCAR from baseline to 180 days was 52% in the combination group.
- Combination therapy led to greater reductions in UCAR at 180 days compared with empagliflozin alone (32% greater) and finerenone alone (29% greater).
- At 180 days, 70% of the patients in the combination group achieved a >30% reduction in UCAR, whereas 52% of the participants in the empagliflozin group and finerenone group achieved this target.
- Greater proportion of patients in the combination group also achieved the target when the threshold was set at 40% or 50% UCAR reduction compared with finerenone or empagliflozin alone (64%, 44% and 43%, respectively, for the 40% threshold; and 55%, 36% and 32%, respectively, for the 50% threshold).
- The incidence of symptomatic hypotension, acute kidney injury, and hyperkalemia leading to drug discontinuation were low.
Conclusion
In the CONFIDENCE trial among patients with CKD and T2D, simultaneous initiation of finerenone and empagliflozin led to a greater reduction in UCAR compared with either finerenone or empagliflozin alone.
- Our reporting is based on the information provided at the ERA Congress 2025 and publication of the study design at ClinicalTrails.gov -