medwireNews: Combination treatment with finerenone and empagliflozin leads to a significantly greater reduction in the urinary albumin-to-creatinine ratio (UACR) than either treatment alone for patients with both chronic kidney disease (CKD) and type 2 diabetes, study findings indicate.
Although the nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium-glucose cotransporter-2 inhibitor empagliflozin are both used in the management of people with CKD and type 2 diabetes, there is limited evidence supporting the simultaneous initiation of the two treatments, say Rajiv Agarwal (Indiana University School of Medicine, Indianapolis, USA) and co-investigators.
To address this, they carried out the international CONFIDENCE trial, which included 800 people with CKD (estimated glomerular filtration rate [eGFR] 30–90 mL/minute per 1.73 m2), albuminuria (UACR 100–≤5000 mg/g), and type 2 diabetes, who were already taking a renin–angiotensin system inhibitor.
The participants were randomly assigned to receive finerenone 10 mg or 20 mg daily according to their eGFR (<60 and ≥60 mL/minute per 1.73 m2, respectively, n=264), empagliflozin 10 mg daily (n=267), or finerenone plus empagliflozin (n=269) for 180 days. Those in the finerenone monotherapy group also received an empagliflozin placebo and vice versa.
At baseline, the median UACR was 578 mg/g in the finerenone group, 583 mg/g in the empagliflozin group, and 574 mg/g in the combination group.
Agarwal et al report in The New England Journal of Medicine that, at day 180, the least squares mean ratio for the change in UACR was 0.68 with finerenone, 0.71 with empagliflozin, and 0.48 with combination therapy.
They comment that this 52% reduction in UACR observed with combination therapy “is in line with the full additive effect that was expected on the basis of the reductions observed with finerenone alone (32%) and empagliflozin alone (29%).”
Of note, 30 days after stopping the trial medication, the UACR had increased in all groups but remained below baseline in the combination and finerenone treatment groups. Specifically, the least squares mean ratio for the change in UACR from day 180 to day 210 was 1.45 with finerenone, 1.44 with empagliflozin, and 1.63 with combination therapy.
The researchers found that there were no unexpected adverse events (AEs) in any of the treatment groups, and serious AEs leading to treatment discontinuation occurred in approximately 1% of participants in each group.
A greater than 30% decline in eGFR at 30 days occurred in fewer patients given finerenone (3.8%) or empagliflozin (1.1%) than in those given the two drugs together (6.3%). However, the authors point out that “the eGFR stabilized after the initial decline, and the incidence of acute kidney injury was uncommon in the combination-therapy group (1.9%) in this trial.”
In conclusion, Agarwal and co-authors speculate “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.”
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