Renal outcomes better with finerenone plus empagliflozin in type 2 diabetes and CKD

Patients with type 2 diabetes and chronic kidney disease (CKD) who are already on a renin-angiotensin system inhibitor and add finerenone plus empagliflozin may have better kidney outcomes than those who add only one of the drugs, according to a recent industry study.

Researchers randomly assigned patients with CKD (estimated glomerular filtration rate [eGFR], 30 to 90 mL/min/1.73 m²), albuminuria (urinary albumin-to-creatinine ratio of 100 to ≤5,000), and type 2 diabetes who were already taking a renin-angiotensin system inhibitor to receive finerenone, 10 or 20 mg/d, empagliflozin, 10 mg/d, or finerenone and empagliflozin. Those randomly assigned to finerenone or empagliflozin also received a placebo matching the other study drug. The study's primary outcome was the relative change in the log-transformed mean urinary albumin-to-creatinine ratio from baseline to 180 days. One of the study authors was a Bayer employee, and Bayer funded the study and was involved in the decision to submit it for publication. Results were published June 5 by the New England Journal of Medicine.

The trial was conducted in North America, Europe, and Asia. Eight hundred patients (269 in the combination group, 264 in the finerenone group, and 267 in the empagliflozin group) were included in the efficacy analyses, and 798 patients (268 in the combination group, 264 in the finerenone group, and 266 in the empagliflozin group) received at least one dose of a trial drug and were included in the safety analyses. Urinary albumin-to-creatinine ratio was similar at baseline in the three groups, with a median value of 579 (interquartile range, 292 to 1,092) among those with available data (265 patients in the combination group, 258 in the finerenone group, and 261 in the empagliflozin group).

At day 180, patients in the combination therapy group had a 29% greater reduction in urinary albumin-to-creatinine ratio than those taking finerenone alone (least-squares mean ratio of the difference in change from baseline, 0.71 [95% CI, 0.61 to 0.82]; P<0.001) and a 32% greater reduction than those taking 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). No unanticipated adverse events were seen. Symptomatic hypotension occurred in three patients in the combination group, while acute kidney injury occurred in five patients in the combination group and three in the finerenone group. One patient in each treatment group discontinued the study medication due to hyperkalemia.

The trial used a surrogate end point, and follow-up was not long enough to measure between-group differences in cardiovascular outcomes or clinical progression of kidney disease, the authors noted. They concluded that in patients with both CKD and type 2 diabetes, initial therapy with finerenone plus empagliflozin more effectively reduced urinary albumin-to-creatinine ratio at 180 days than either of the two drugs alone. These reductions, along with previous data, suggest “that the reductions observed with combination therapy with empagliflozin and finerenone will probably correlate with meaningful reductions in the risk of progression of chronic kidney disease,” the authors wrote.