Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study

Abstract Background Sodium–glucose co-transporter 2 (SGLT2) inhibitors offer cardiovascular benefits in patients with heart failure, yet their direct effects on myocardial fibrosis—particularly in heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D)—remain underexplored....

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Main Authors: Arif Albulushi, Kimia M. Askari, Ammar M. Al-Abedi, Malak A. Al-Kulaibi, Murtadha S. Hasan, Zahra Hosseini, Mezon T. Al-Rahman, Desmond B. Tanoh, Amjad S. Hasan, Yaseen Al-Helli, Ahmed Basouni
Format: Article
Language:English
Published: BMC 2025-07-01
Series:European Journal of Medical Research
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Online Access:https://doi.org/10.1186/s40001-025-02834-7
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author Arif Albulushi
Kimia M. Askari
Ammar M. Al-Abedi
Malak A. Al-Kulaibi
Murtadha S. Hasan
Zahra Hosseini
Mezon T. Al-Rahman
Desmond B. Tanoh
Amjad S. Hasan
Yaseen Al-Helli
Ahmed Basouni
author_facet Arif Albulushi
Kimia M. Askari
Ammar M. Al-Abedi
Malak A. Al-Kulaibi
Murtadha S. Hasan
Zahra Hosseini
Mezon T. Al-Rahman
Desmond B. Tanoh
Amjad S. Hasan
Yaseen Al-Helli
Ahmed Basouni
author_sort Arif Albulushi
collection DOAJ
description Abstract Background Sodium–glucose co-transporter 2 (SGLT2) inhibitors offer cardiovascular benefits in patients with heart failure, yet their direct effects on myocardial fibrosis—particularly in heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D)—remain underexplored. This study investigates the antifibrotic impact of dapagliflozin in diabetic HFpEF patients, with a focus on its potential as a disease-modifying therapy. Methods In a multicenter, double-blind, placebo-controlled trial, 100 patients with HFpEF and T2D were randomized (1:1) to receive dapagliflozin 10 mg daily or placebo for 12 months. Stratification was performed by baseline extracellular volume fraction (ECV). Myocardial fibrosis was assessed using cardiac MRI-derived ECV at baseline, 6 months, and 12 months. Secondary endpoints included changes in left ventricular mass index (LVMI), HbA1c, and 6-min walk test (6MWT) distance. Results Dapagliflozin significantly reduced myocardial fibrosis (mean ΔECV: − 3.5% [95% CI − 4.2 to − 2.8]) compared to placebo (− 0.8% [95% CI − 1.3 to − 0.4]; p < 0.001). Additional benefits included greater reductions in LVMI (− 8.2 g/m2 vs. − 2.1 g/m2; p = 0.002), improved glycemic control (HbA1c: − 1.2% vs. − 0.4%; p = 0.01), and enhanced functional capacity (+ 45 m vs. + 10 m in 6MWT; p = 0.01). Conclusions Dapagliflozin demonstrated a significant reduction in myocardial fibrosis and improvements in cardiac structure, metabolic control, and exercise tolerance in HFpEF patients with T2D. These findings support the evolving role of SGLT2 inhibitors as validated components of guideline-directed therapy, with potential disease-modifying effects through targeted myocardial fibrosis regression.
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spelling doaj-art-b25ff636b48644819d4f9fdfd151808a2025-08-20T04:01:53ZengBMCEuropean Journal of Medical Research2047-783X2025-07-013011910.1186/s40001-025-02834-7Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal studyArif Albulushi0Kimia M. Askari1Ammar M. Al-Abedi2Malak A. Al-Kulaibi3Murtadha S. Hasan4Zahra Hosseini5Mezon T. Al-Rahman6Desmond B. Tanoh7Amjad S. Hasan8Yaseen Al-Helli9Ahmed Basouni10Department of Adult Cardiology, National Heart Center, The Royal HospitalDepartment of Adult Cardiology, National Heart Center, The Royal HospitalDepartment of Adult Cardiology, National Heart Center, The Royal HospitalDepartment of Adult Cardiology, National Heart Center, The Royal HospitalDepartment of Adult Cardiology, National Heart Center, The Royal HospitalDepartment of Radiology, Oman International HospitalDepartment of Family Medicine, Al-Khuwair Health CenterDepartment of Medicine, Insight Hospital and Medical Center ChicagoDepartment of Medicine, Kasr Alaini HospitalCollege of Medicine and Health Sciences, National University of Science and TechnologyDepartment of Cardiology, Sultan Qaboos Comprehensive Cancer Care and Research CentreAbstract Background Sodium–glucose co-transporter 2 (SGLT2) inhibitors offer cardiovascular benefits in patients with heart failure, yet their direct effects on myocardial fibrosis—particularly in heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D)—remain underexplored. This study investigates the antifibrotic impact of dapagliflozin in diabetic HFpEF patients, with a focus on its potential as a disease-modifying therapy. Methods In a multicenter, double-blind, placebo-controlled trial, 100 patients with HFpEF and T2D were randomized (1:1) to receive dapagliflozin 10 mg daily or placebo for 12 months. Stratification was performed by baseline extracellular volume fraction (ECV). Myocardial fibrosis was assessed using cardiac MRI-derived ECV at baseline, 6 months, and 12 months. Secondary endpoints included changes in left ventricular mass index (LVMI), HbA1c, and 6-min walk test (6MWT) distance. Results Dapagliflozin significantly reduced myocardial fibrosis (mean ΔECV: − 3.5% [95% CI − 4.2 to − 2.8]) compared to placebo (− 0.8% [95% CI − 1.3 to − 0.4]; p < 0.001). Additional benefits included greater reductions in LVMI (− 8.2 g/m2 vs. − 2.1 g/m2; p = 0.002), improved glycemic control (HbA1c: − 1.2% vs. − 0.4%; p = 0.01), and enhanced functional capacity (+ 45 m vs. + 10 m in 6MWT; p = 0.01). Conclusions Dapagliflozin demonstrated a significant reduction in myocardial fibrosis and improvements in cardiac structure, metabolic control, and exercise tolerance in HFpEF patients with T2D. These findings support the evolving role of SGLT2 inhibitors as validated components of guideline-directed therapy, with potential disease-modifying effects through targeted myocardial fibrosis regression.https://doi.org/10.1186/s40001-025-02834-7HFpEFMyocardial fibrosisDapagliflozinSGLT2 inhibitorsType 2 diabetesCardiac MRI
spellingShingle Arif Albulushi
Kimia M. Askari
Ammar M. Al-Abedi
Malak A. Al-Kulaibi
Murtadha S. Hasan
Zahra Hosseini
Mezon T. Al-Rahman
Desmond B. Tanoh
Amjad S. Hasan
Yaseen Al-Helli
Ahmed Basouni
Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study
European Journal of Medical Research
HFpEF
Myocardial fibrosis
Dapagliflozin
SGLT2 inhibitors
Type 2 diabetes
Cardiac MRI
title Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study
title_full Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study
title_fullStr Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study
title_full_unstemmed Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study
title_short Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study
title_sort impact of sglt2 inhibitors on myocardial fibrosis in diabetic hfpef a longitudinal study
topic HFpEF
Myocardial fibrosis
Dapagliflozin
SGLT2 inhibitors
Type 2 diabetes
Cardiac MRI
url https://doi.org/10.1186/s40001-025-02834-7
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