Safety and Synergy of Finerenone and Empagliflozin in Lowering Blood Pressure

Agarwal R, Correa-Rotter R, Navaneethan SD, Heerspink HJ, Weir MR, McGill JB, Mottl AK, Nangaku M, Rosenstock J, Rossing P, Vaduganathan M, Scott C, Li L, Brinker M, Kovesdy CP, Green JB, Mann J (2026)

Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1161/HYPERTENSIONAHA.126.27036

Abstract

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.

Involved external institutions

University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) University of Maryland School of Pharmacy United States (USA) (US) Washington University in St. Louis United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) University of Copenhagen Denmark (DK) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Bayer Corporation United States (USA) (US) Bayer AG Germany (DE) The University of Tennessee Health Science Center United States (USA) (US) Duke University Health System United States (USA) (US) Indiana University – Purdue University Indianapolis United States (USA) (US) National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ) / Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) Mexico (MX) Baylor College of Medicine United States (USA) (US)

How to cite

APA:

Agarwal, R., Correa-Rotter, R., Navaneethan, S.D., Heerspink, H.J., Weir, M.R., McGill, J.B.,... Mann, J. (2026). Safety and Synergy of Finerenone and Empagliflozin in Lowering Blood Pressure. Hypertension. https://doi.org/10.1161/HYPERTENSIONAHA.126.27036

MLA:

Agarwal, Rajiv, et al. "Safety and Synergy of Finerenone and Empagliflozin in Lowering Blood Pressure." Hypertension (2026).

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