Limited evidence exists to support the simultaneous initiation of sodium-glucose cotransporter-2 inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in persons with chronic kidney disease and type 2 diabetes.

We randomly assigned participants with chronic kidney disease (estimated glomerular filtration rate [eGFR], 30 to 90 ml per minute per 1.73 m of body-surface area), albuminuria (a urinary albumin-to-creatinine ratio of 100 to ≤5000 [with albumin measured in milligrams and creatinine measured in grams]), and type 2 diabetes, who were already taking a renin-angiotensin system inhibitor, in a 1:1:1 ratio to receive finerenone (with empagliflozin-matching placebo) at a dose of 10 or 20 mg per day, empagliflozin at a dose of 10 mg per day (with finerenone-matching placebo), or a combination of finerenone and empagliflozin. The primary outcome was the relative change in the log-transformed mean urinary albumin-to-creatinine ratio from baseline to 180 days. Safety was assessed.

At baseline, the urinary albumin-to-creatinine ratio was similar among the participants in the three groups; the median value was 579 (interquartile range, 292 to 1092) among those with available data (265 in the combination-therapy group, 258 in the finerenone group, and 261 participants in the empagliflozin group). At day 180, the reduction in the urinary albumin-to-creatinine ratio with combination therapy was 29% greater than that with finerenone alone (least-squares mean ratio of the difference in the change from baseline, 0.71; 95% confidence interval [CI], 0.61 to 0.82; P<0.001) and 32% greater than that with empagliflozin alone (least-squares mean ratio of the difference in the change from baseline, 0.68; 95% CI, 0.59 to 0.79; P<0.001). Neither agent, alone or in combination, led to unexpected adverse events. Symptomatic hypotension, acute kidney injury, and hyperkalemia leading to drug discontinuation were uncommon.

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. (Funded by Bayer; CONFIDENCE ClinicalTrials.gov number, NCT05254002.).