JCI insight · 2023
Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Fan Li-Chao, McConn Keith, Plataki Maria, Kenny Sarah, Williams Niamh C, Kim Kihwan, Quirke Jennifer A, Chen Yan, Sauler Maor, Möbius Matthias E, Chung Kuei-Pin, Area Gomez Estela, Choi Augustine Mk, Xu Jin-Fu, Cloonan Suzanne M
Аннотация
OBJECTIVE: The CONFIDENCE trial demonstrated additive benefits of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and a sodium-glucose cotransporter 2 (SGLT2) inhibitor compared with monotherapy in reducing the urinary albumin-to-creatinine ratio (UACR). This prespecified analysis evaluated whether safety and efficacy of combination therapy varies by baseline glucagon-like peptide 1 receptor agonist (GLP-1 RA) use.
RESEARCH DESIGN AND METHODS: Adults with chronic kidney disease (UACR ≥100 to <5,000 mg/g; estimated glomerular filtration rate [eGFR] 30-90 mL/min/1.73 m2) and type 2 diabetes (glycated hemoglobin <11% [97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin.
RESULTS: Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline in participants using a GLP-1 RA was -51% (95% CI -59 to -40%) with combination therapy, -34% (-48 to -18%) with finerenone, and -36% (-48 to -21%) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were -56% (-62 to -50%), -37% (-45 to -28%), and -33% (-41 to -23%), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed and were more pronounced with combination therapy.
CONCLUSIONS: In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA.
RESEARCH DESIGN AND METHODS: Adults with chronic kidney disease (UACR ≥100 to <5,000 mg/g; estimated glomerular filtration rate [eGFR] 30-90 mL/min/1.73 m2) and type 2 diabetes (glycated hemoglobin <11% [97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin.
RESULTS: Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline in participants using a GLP-1 RA was -51% (95% CI -59 to -40%) with combination therapy, -34% (-48 to -18%) with finerenone, and -36% (-48 to -21%) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were -56% (-62 to -50%), -37% (-45 to -28%), and -33% (-41 to -23%), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed and were more pronounced with combination therapy.
CONCLUSIONS: In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA.