Among persons with chronic kidney disease (CKD) and type 2 diabetes (T2D), combination therapy with finerenone plus empagliflozin leads to a greater reduction in the urinary albumin-to-creatinine ratio (UACR) than either drug alone, according to results from the CONFIDENCE trial published June 5 in the New England Journal of Medicine.

In this double-blind multicenter trial, Rajiv Agarwal, MD, FACC, et al., randomized 800 patients (mean age 66 years, 25% women) to receive 10 or 20 mg of finerenone once daily (with empagliflozin-matching placebo), 10 mg of empagliflozin once daily (with finerenone-matching placebo), or a combination of finerenone plus empagliflozin. All patients were also taking a renin-angiotensin system inhibitor.

At baseline, participants had an estimated glomerular filtration rate (eGFR) between 30 and 90 mL/min/1.73 m², a UACR of 100 to ≤5,000 (median UACR 579) and glycated hemoglobin <11%.

Results showed that at 180 days, reduction in UACR was 29% greater with finerenone plus empagliflozin vs. finerenone alone (least-squares [LS] mean ratio 0.71) and 32% greater vs. empagliflozin alone (LS mean ratio 0.68) (p<0.001 for both).

Notably, the UACR was reduced by 52% in the combination-therapy group from baseline to day 180 (LS mean ratio 0.48). Indeed, more patients achieved UACR reductions >30%, >40% and >50% with combination therapy vs. either treatment alone.

In other findings, reduction in UACR was fast, with those in the combination-therapy group achieving a >30% drop from baseline after 14 days and >40% after 90 days. When therapy was stopped during a 30-day washout period, UACR levels increased but remained below baseline in the combination and finerenone therapy groups.

Regarding safety, the mean increase in serum potassium was 0.27 mmol/L after 14 days for combination therapy but declined to near baseline levels 30 days after the trial treatment ended. Moreover, there was an early decline in both eGFR and systolic blood pressure, which generally rebounded with drug discontinuation. Symptomatic hypotension, acute kidney injury and hyperkalemia were rare in this trial.

Agarwal and colleagues write that although longer follow-up is needed, "these data suggest that the reductions observed with combination therapy ... will probably correlate with meaningful reductions in the risk of progression of CKD."