Short-term superiority in proteinuria control with exploratory longitudinal trajectories: finerenone-dapagliflozin combination in non-diabetic kidney disease
5 affiliations
- 1Department of Pharmacy, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine
- 2Department of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University
- 3Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
- 4Department of Stomatology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
- 5Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University
Abstract
Introduction: Finerenone and dapagliflozin have demonstrated renal protective effects in diabetic kidney disease, but real-world evidence on their combination in non-diabetic kidney disease (NDKD) remains scarce. We assessed whether their combination improves short-term proteinuria control versus monotherapy, with long-term trajectories explored as hypothesis-generating outcomes.
Methods: This retrospective cohort study included 327 NDKD patients admitted to Nanjing Drum Tower Hospital (January 2022–March 2026). Patients were divided into three groups: finerenone monotherapy, dapagliflozin monotherapy, or combination therapy. Propensity score matching (PSM) was used to balance baseline characteristics. Short-term (3 months) efficacy, safety, and exploratory cost analysis were compared. Longitudinal data were analyzed using generalized estimating equations (GEE), with the primary inferential window at 3–6 months and a sensitivity analysis at 3–24 months. Multivariate logistic regression identified predictors of treatment failure in the full unmatched cohort. Exploratory subgroup analyses were performed in membranous nephropathy and hypertension.
Results: After PSM, at 3 months, combination therapy achieved a higher overall remission rate than dapagliflozin monotherapy (69.57% vs. 39.13%, OR = 3.56, 95% CI: 1.50–8.40, P = 0.003), but not versus finerenone monotherapy (68.29% vs. 51.22%, OR = 2.05, 95% CI: 0.84–5.05, P = 0.115). In the primary 3–6 months GEE analysis, time effects were significant for clinical remission rates and proteinuria; Sensitivity GEE analysis (3–24 months) was consistent. Descriptive analyses from 3 to 24 months showed numerical improvement trends across groups, but these are exploratory. Adverse event rates were low, but the analysis was underpowered to exclude increased hyperkalemia risk. In exploratory cost analysis, the ICER was 22.99 RMB per 1% increase in remission rate versus finerenone and 20.79 RMB versus dapagliflozin; probabilistic sensitivity analysis was broadly consistent with the base case, without judgment of economic superiority. Dapagliflozin monotherapy was independently associated with treatment failure (OR = 2.163, 95% CI: 1.073–4.362, P = 0.031) in the full unmatched cohort. Exploratory subgroup analyses suggested potential benefit in membranous nephropathy and hypertension.
Conclusion: Finerenone combined with dapagliflozin provides higher observed short-term (3 months) efficacy in NDKD, with low observed adverse event rates. Long-term outcomes require validation in larger prospective studies.
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BibTeX
@article{zhu2026shortterm,
title = {{Short-term superiority in proteinuria control with exploratory longitudinal trajectories: finerenone-dapagliflozin combination in non-diabetic kidney disease}},
author = {Mali Zhu and Yingyi Deng and Lijun Su and Haixia Zhang and Yun Yang and Lulu Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1918911},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1918911/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Short-term superiority in proteinuria control with exploratory longitudinal trajectories: finerenone-dapagliflozin combination in non-diabetic kidney disease
AU - Mali Zhu
AU - Yingyi Deng
AU - Lijun Su
AU - Haixia Zhang
AU - Yun Yang
AU - Lulu Wang
PY - 2026
DA - 2026/10/13
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1918911
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1918911/full
AB - Introduction: Finerenone and dapagliflozin have demonstrated renal protective effects in diabetic kidney disease, but real-world evidence on their combination in non-diabetic kidney disease (NDKD) remains scarce. We assessed whether their combination improves short-term proteinuria control versus monotherapy, with long-term trajectories explored as hypothesis-generating outcomes. Methods: This retrospective cohort study included 327 NDKD patients admitted to Nanjing Drum Tower Hospital (January 2022–March 2026). Patients were divided into three groups: finerenone monotherapy, dapagliflozin monotherapy, or combination therapy. Propensity score matching (PSM) was used to balance baseline characteristics. Short-term (3 months) efficacy, safety, and exploratory cost analysis were compared. Longitudinal data were analyzed using generalized estimating equations (GEE), with the primary inferential window at 3–6 months and a sensitivity analysis at 3–24 months. Multivariate logistic regression identified predictors of treatment failure in the full unmatched cohort. Exploratory subgroup analyses were performed in membranous nephropathy and hypertension. Results: After PSM, at 3 months, combination therapy achieved a higher overall remission rate than dapagliflozin monotherapy (69.57% vs. 39.13%, OR = 3.56, 95% CI: 1.50–8.40, P = 0.003), but not versus finerenone monotherapy (68.29% vs. 51.22%, OR = 2.05, 95% CI: 0.84–5.05, P = 0.115). In the primary 3–6 months GEE analysis, time effects were significant for clinical remission rates and proteinuria; Sensitivity GEE analysis (3–24 months) was consistent. Descriptive analyses from 3 to 24 months showed numerical improvement trends across groups, but these are exploratory. Adverse event rates were low, but the analysis was underpowered to exclude increased hyperkalemia risk. In exploratory cost analysis, the ICER was 22.99 RMB per 1% increase in remission rate versus finerenone and 20.79 RMB versus dapagliflozin; probabilistic sensitivity analysis was broadly consistent with the base case, without judgment of economic superiority. Dapagliflozin monotherapy was independently associated with treatment failure (OR = 2.163, 95% CI: 1.073–4.362, P = 0.031) in the full unmatched cohort. Exploratory subgroup analyses suggested potential benefit in membranous nephropathy and hypertension. Conclusion: Finerenone combined with dapagliflozin provides higher observed short-term (3 months) efficacy in NDKD, with low observed adverse event rates. Long-term outcomes require validation in larger prospective studies.
SN - 1663-9812
ER -