A randomized controlled trial demonstrated that simultaneous initiation of finerenone and empagliflozin led to significantly greater reductions in the urinary albumin-to-creatinine ratio (UACR) compared with either therapy alone in patients with chronic kidney disease and type 2 diabetes.
The CONFIDENCE trial, a multinational, double-blind study, randomized 800 participants with chronic kidney disease (estimated glomerular filtration rate [eGFR], 30–90 mL/min/1.73 m²), albuminuria (UACR, 100–5000 mg/g), and type 2 diabetes who were already receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. Patients were assigned to receive finerenone alone, empagliflozin alone, or combination therapy for 180 days.
Primary Efficacy Outcomes
At day 180, combination therapy reduced UACR by 29% more than finerenone alone (least-squares mean [LSM] ratio, 0.71; 95% CI, 0.61–0.82; P<.001) and by 32% more than empagliflozin alone (LSM ratio, 0.68; 95% CI, 0.59–0.79; P<.001).
The LSM ratio of change from baseline to day 180 was:
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0.48 (95% CI, 0.44–0.54) with combination therapy (52% reduction),
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0.68 (95% CI, 0.61–0.76) with finerenone alone (32% reduction),
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0.71 (95% CI, 0.64–0.79) with empagliflozin alone (29% reduction).
Secondary Efficacy Outcomes
At day 180, more patients in the combination group achieved clinically meaningful UACR reductions:
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A reduction of more than 30% was achieved by 168 of 240 patients (70.0%) compared with 123 of 236 (52.1%) in the finerenone group and 123 of 238 (51.7%) in the empagliflozin group.
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A reduction of more than 40% occurred in 154 of 240 patients (64.2%) compared with 104 of 236 (44.1%) and 103 of 238 (43.3%), respectively.
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A reduction of more than 50% was achieved by 131 of 240 patients (54.6%) compared with 84 of 236 (35.6%) and 76 of 238 (31.9%).
Safety Profile and Adverse Events
No unexpected safety signals were observed. Serious adverse events occurred in:
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19 of 268 patients (7.1%) in the combination group,
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16 of 264 (6.1%) in the finerenone group,
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17 of 266 (6.4%) in the empagliflozin group.
Hyperkalemia was reported in:
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25 of 268 patients (9.3%) in the combination group,
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30 of 264 (11.4%) in the finerenone group,
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10 of 266 (3.8%) in the empagliflozin group.
Serum potassium concentrations greater than 5.5 mmol/L occurred in:
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40 of 262 patients (15.3%) in the combination group,
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48 of 258 (18.6%) in the finerenone group,
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25 of 257 (9.7%) in the empagliflozin group.
Renal Function and Blood Pressure Effects
An eGFR decline of more than 30% at day 30 was reported in:
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17 patients (6.3%) in the combination group,
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10 (3.8%) in the finerenone group,
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3 (1.1%) in the empagliflozin group.
Most eGFR declines were reversible following treatment discontinuation. Systolic blood pressure decreased by approximately 7.4 mmHg with combination therapy, a change that reversed after discontinuation.
Baseline Characteristics
The trial population had a mean age of 66.5 ± 10.3 years; 198 of 800 patients (24.8%) were female. The mean baseline eGFR was 54.2 ± 17.1 mL/min/1.73 m². Median UACR was 579 mg/g (interquartile range, 292–1092), and 787 of 800 participants (98.4%) were receiving an ACE inhibitor or angiotensin receptor blocker at baseline.
Clinical Context and Conclusion
According to researchers, “the time course of the changes in the urinary albumin-to-creatinine ratio suggests that most of the reduction occurred within 4 weeks after the initiation of therapy.” They noted that a 30% reduction in UACR is associated with a 27% lower risk of a composite kidney outcome, including end-stage kidney disease, doubling of serum creatinine concentration, or an eGFR less than 15 mL/min/1.73 m².
The authors concluded: “Among persons with both chronic kidney disease and type 2 diabetes, initial therapy with finerenone plus empagliflozin led to a greater reduction in the urinary albumin-to-creatinine ratio than either treatment alone.”
The study was funded by Bayer and registered at ClinicalTrials.gov (NCT05254002).