Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE).
The phase 2 CONFIDENCE trial tested whether simultaneously starting finerenone and the SGLT2 inhibitor empagliflozin lowers albuminuria more than either agent alone in chronic kidney disease and type 2 diabetes; combination therapy produced a greater reduction in urine albumin-to-creatinine ratio at 6 months than either monotherapy.
Background
Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, and SGLT2 inhibitors each reduce chronic kidney disease progression and improve kidney and cardiovascular outcomes in type 2 diabetes, but it has been unclear whether the two should be initiated sequentially or simultaneously. CONFIDENCE was designed to test the hypothesis that early combination therapy is superior to either drug alone for reducing albuminuria.
Study design
CONFIDENCE (NCT05254002) is a randomized, double-blind, double-dummy, multicentre phase 2 trial in adults with chronic kidney disease and type 2 diabetes, eGFR 30 to 90 mL/min/1.73m2, and urine albumin-to-creatinine ratio of 100 to under 5000 mg/g, all on a maximally tolerated renin-angiotensin system inhibitor. A total of 818 participants across 143 sites in 14 countries were randomized 1:1:1 to once-daily finerenone plus empagliflozin, finerenone plus placebo, or empagliflozin plus placebo, with the primary outcome the relative change in urine albumin-to-creatinine ratio from baseline at day 180. At baseline mean eGFR was 54.2 mL/min/1.73m2 and median UACR was 583 mg/g.
Key findings
At day 180, the reduction in urine albumin-to-creatinine ratio with combination therapy was about 29% greater than with finerenone alone and about 32% greater than with empagliflozin alone, both statistically significant. The combination was generally well tolerated, with symptomatic hypotension, acute kidney injury, and hyperkalemia leading to drug discontinuation reported as uncommon, and no unexpected adverse events.
Clinical implications
CONFIDENCE supports that simultaneous initiation of finerenone and an SGLT2 inhibitor yields an additive albuminuria-lowering effect beyond either agent alone in patients with type 2 diabetes and albuminuric chronic kidney disease. Because albuminuria reduction is a recognised surrogate for kidney disease progression, these results inform an early, combined treatment strategy, though longer-term effects on hard kidney and cardiovascular outcomes require dedicated outcome trials.
Category
Research
Source
Nephrol Dial Transplant
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