Key result
Finerenone plus empagliflozin yields ~83% higher odds of clinically meaningful SBP reduction vs finerenone alone.
Why the study?
This study assessed SBP changes with empagliflozin/finerenone combination therapy versus monotherapy in people with CKD and type 2 diabetes across baseline SBP categories, as well as predictors of SBP response and mediation of UACR reductions.
Does combination therapy with finerenone and empagliflozin safely improve systolic blood pressure compared to monotherapy in patients with chronic kidney disease and type 2 diabetes?
RCT (n=800)
Double-blind
1:1:1 ratio
Yes
Does combination therapy with finerenone and empagliflozin safely improve systolic blood pressure compared to monotherapy in patients with chronic kidney disease and type 2 diabetes?
Combination therapy with finerenone and empagliflozin provides additive blood pressure lowering in patients with elevated systolic blood pressure while remaining safe in those with baseline SBP <130 mm Hg.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The CONFIDENCE study delivers the clear message that simultaneous initiation of finerenone and empagliflozin led to an early and additive reduction in UACR of 52% in patients with CKD and T2D, which was significantly greater than with either treatment alone. In other chronic conditions like heart failure or hypertension, we're moving away from the traditional stepwise approach toward upfront combination therapy. In CONFIDENCE, 70% of patients on both therapies achieved the ADA-recommended UACR reduction target of >30%.”
Favors combination finerenone-empagliflozin for additive systolic blood pressure reduction when baseline SBP ≥130 mm Hg; extends CONFIDENCE trial findings beyond UACR.
BACKGROUND: This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions. METHODS: Participants (n=800) were stratified by baseline SBP (<130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction. RESULTS: At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) had SBP <130 mm Hg. Combination therapy increased SBP response odds versus finerenone (odds ratio, 1.83 [95% CI, 1.21–2.76]; P =0.004) or empagliflozin (odds ratio, 1.45 [95% CI, 0.97–2.17]; P =0.07). The strongest predictor of response was baseline SBP (odds ratio, 2.04 per 10 mm Hg higher SBP; P <0.0001). Combination therapy significantly reduced SBP versus monotherapies in the ≥130 mm Hg ( P <0.0001) but not in the <130 mm Hg group. SBP reduction mediated <10% of the total urinary albumin-to-creatinine ratio reduction. Acute kidney injury and hyperkalemia incidences were similar across SBP subgroups. CONCLUSIONS: Combination therapy reduced SBP more than monotherapies in participants with SBP ≥130 mm Hg. Urinary albumin-to-creatinine ratio reduction appeared largely independent of SBP changes at day 30; though this secondary analysis was limited by reliance on clinic blood pressure measurement. Prospective studies with ambulatory blood pressure monitoring are required.
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Agarwal et al. (2026) conducted an RCT in Chronic kidney disease and type 2 diabetes (n=800). Combination therapy (finerenone and empagliflozin) vs. Finerenone alone or empagliflozin alone was evaluated on Systolic blood pressure response (≥10 mm Hg reduction from baseline at day 180) vs finerenone (OR 1.83, 95% CI 1.21-2.76, p=0.004). Combination therapy with finerenone and empagliflozin significantly increased the odds of achieving a systolic blood pressure reduction of ≥10 mm Hg at day 180 compared to finerenone alone (OR 1.83).
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