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.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Nephrology | |
| Internal Medicine |  |
| Endocrine | |
The reason for only a 4 rating for relevance is my assumption that if either an SGLT-2 inhibitor or an MRA alone did not markedly lower UACR, the other would be added (producing the combination) regardless of the presence or not of a GLP-1 agonist.
No effect on proteinuria noted. Is the question answered by this study?
It is useful to understand the relative benefits of albuminuria reduction by the combination of various antidiabetic and antialbuminuric medications. This study nicely shows the combined efficacy of MRB and SGLT2i, with limited additional benefit from GLP-1 RA strictly from the standpoint of albuminuria reduction. This does not necessarily eliminate the other benefits of GLP-1 RA, but puts the renal expectations into perspective.
Newsworthy but small numbers with inherent differences in patients on a GLP1-RA vs not makes it difficult to draw definite conclusions.
In a cohort with a mean eGFR of 54.2 mL/min/1.73m² (SD 17.1) and a UACR range of 292–1092, this study demonstrated that combination therapy with an MRA and an SGLT-2 inhibitor resulted in an additive reduction in proteinuria at 180 days of follow-up compared with monotherapy, independent of concomitant GLP-1 receptor agonist use. These findings provide RCT evidence supporting the clinical effectiveness of combining two agents that are already widely used in practice. The incidence and severity of hyperkalemia were comparable to those observed with finerenone monotherapy. At 30 days, systolic blood pressure decreased by approximately 2.5 mmHg with each monotherapy, whereas the combination therapy produced a greater reduction of about 10 mmHg.