Additive effects of dapagliflozin and finerenone on albuminuria in non-diabetic CKD: an open-label randomized clinical trial

Abstract

Background. Dapagliflozin and finerenone reduce albuminuria and slow CKD progression, but additive effects remain unstudied. We compared their individual and combined efficacy and safety in patients with non-diabetic CKD. Methods. In an open-label, randomized clinical trial, we included patients aged 18–80 on maximal tolerated ACE inhibitor or angiotensin receptor blocker with eGFR 25–45 mL/min/1,73 m2 and albuminuria 150–2000 mg/g. Participants received either finerenone 20 mg/day or dapagliflozin 10 mg/day for four weeks, followed by combination therapy for four weeks. Data were collected at baseline, 4 and 8 weeks. Results. Twenty patients (10 per group) with a mean mGFR of 34 mL/min/1,73 m2 and a mean urine albumin creatinine ratio (UACR) of 469 mg/g were included. Finerenone alone or in addition to dapagliflozin resulted in −24% (95% CI, −36% to −11%) and −34% (95% CI, −47% to −18%) change in UACR, respectively. Dapagliflozin alone or in addition to finerenone resulted in −8% (95% CI, −22 to 9%) and −10% (95% CI, −28% to 12%) change in UACR, respectively. Overall, UACR change after 8 weeks was −36% (95% CI, −46% to −24%). After 8 weeks, systolic blood pressure and mGFR were reduced by 10 mmHg (95% CI, 6–13 mmHg) and 7 mL/min/1,73 m2 (95% CI, 5–8 mL/min/1,73 m2). Adverse effects were minimal. Conclusions. The combination of finerenone and dapagliflozin was safe and significantly reduced albuminuria. The effect of combination therapy was at least equal to the calculated, combined effect of each of the drugs, suggesting an additive effect on albuminuria. Larger studies assessing long-term effects and safety are warranted.