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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BMC
2025-07-01
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| 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. |
| format | Article |
| id | doaj-art-b25ff636b48644819d4f9fdfd151808a |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| 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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