Impact of Simultaneous Initiation of Finerenone and Empagliflozin on Albuminuria Irrespective of Baseline HbA1c Levels: A Participant-Level Exploratory Analysis of the Randomised CONFIDENCE Trial

Aims: This prespecified analysis evaluated whether the safety and efficacy of finerenone and a sodium–glucose cotransporter 2 inhibitor (SGLT2i) combination vary by baseline glycated haemoglobin (HbA1c). Materials and Methods: Adults with type 2 diabetes and a urinary albumin-to-creatinine ratio (UACR) of 100 − < 5000 mg/g, estimated glomerular filtration rate (eGFR) 30–90 mL/min/1.73 m² and HbA1c < 11% (< 97 mmol/mol) were randomised (1:1:1) to once-daily finerenone, empagliflozin or combination. Primary outcome was UACR change from baseline at Day 180. Results: Baseline HbA1c was available for 781/800 CONFIDENCE participants; baseline HbA1c and eGFR mean values (standard deviation) were 7.3% (1.2%) and 54.2 mL/min/1.73 m² (17.1 mL/min/1.73 m²). At Day 180, HbA1c decreased with combination therapy and empagliflozin (both least-squares mean change −0.1% [95% confidence interval −0.2, −0.0]), with no change with finerenone. In total, 212, 190, 188 and 191 participants were included in HbA1c Quartiles 1 (HbA1c ≤ 6.4% [≤ 46 mmol/mol]), 2 (HbA1c > 6.4 and ≤ 7.1% [> 46 and ≤ 54 mmol/mol]), 3 (HbA1c > 7.1 and ≤ 7.9% [> 54 and ≤ 63 mmol/mol]) and 4 (HbA1c > 7.9% [> 63 mmol/mol]), respectively. Change from baseline in HbA1c at Day 180 was greatest in Quartile 4. At Day 180, combination therapy reduced UACR from baseline in all HbA1c quartiles to a greater extent than either monotherapy (mean [95% CI] –53% [−63, −42], −47% [−57, −34], −63% [−70, −54] and −55% [−65, −42], in Quartiles 1–4, respectively). Conclusion: Simultaneous initiation with finerenone and an SGLT2i reduced UACR compared with monotherapy and was well-tolerated irrespective of HbA1c levels.