SGLT2 Inhibitors and Cardiovascular Outcomes in Patients With Fabry Disease: Observations From a Federated Research Network
9 affiliations
- 1Institute of Life Course and Medical Sciences University of Liverpool Liverpool UK
- 2Department of Life, Health and Environmental Sciences University of L'Aquila L'Aquila Italy
- 3Internal Medicine and Nephrology Division, ASL1 Avezzano‐Sulmona‐L'Aquila, San Salvatore Hospital L'Aquila Italy
- 4Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia, Policlinico di Modena Modena Italy
- 5Clinical and Experimental Medicine PhD Program University of Modena and Reggio Emilia Modena Italy
- 6Internal, Vascular and Emergency Medicine—Stroke Unit University of Perugia Perugia Italy
- 7Infiltrative Cardiomyopathy Program, Division of Cardiology University of Louisville Louisville Kentucky USA
- 8Danish Center for Health Services, Department of Clinical Medicine Aalborg University Aalborg Denmark
- 9Department of Cardiology, Lipidology and Internal Medicine With Intensive Coronary Care Unit Medical University of Bialystok Bialystok Poland
Abstract
Background and Aim: Fabry disease (FD) is frequently complicated by renal impairment and cardiovascular events; however, evidence on sodium–glucose cotransporter‐2 inhibitors (SGLT2i) in this population is scarce. Accordingly, we assessed the association between SGLT2i exposure and cardiovascular outcomes in adults with FD.
Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adults with Fabry disease and eGFR ≥ 20 mL/min/1.73 m2, excluding Type 1 diabetes. Patients were stratified by SGLT2 inhibitor exposure. The primary outcome was a composite of all‐cause death, acute myocardial infarction and acute or acute‐on‐chronic heart failure at 2 and 5 years; secondary outcomes included individual components and progression to advanced kidney disease. Patients with prior non‐fatal outcomes were excluded from the respective analyses. Propensity score matching (1:1) and Cox proportional hazards models were used. Sensitivity analyses included alternative follow‐up periods, restriction to Fabry disease diagnosed from 2013 onwards and a stricter Fabry disease definition requiring ≥ 2 diagnoses; subgroup analyses were performed by sex and age.
Results: Among 14 940 FD patients, 1028 (6.9%) had recorded exposure to SGLT2 inhibitors (mean age: 65.5 ± 12.0 years; 53.0% male), who were older and had a higher comorbidity burden and worse baseline renal profile than non‐exposed patients. After PSM, 732 patients per group (exposed and non‐exposed patients) were available for analysis. At 2 years, SGLT2i exposure was associated with a lower risk of the composite outcome (HR 0.61; 95% CI 0.38–0.97) and all‐cause death (HR 0.56; 95% CI 0.33–0.95). At 5 years, results were consistent for the composite outcome (HR 0.56; 95% CI 0.39–0.79) and all‐cause death (HR 0.62; 95% CI 0.42–0.93), with reduced myocardial infarction risk (HR 0.53; 95% CI 0.30–0.90).
Conclusions: In a large real‐world FD cohort, SGLT2i exposure was associated with lower cardiovascular risk and mortality, supporting further prospective investigation.
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BibTeX
@article{serio2026sglt2,
title = {{SGLT2 Inhibitors and Cardiovascular Outcomes in Patients With Fabry Disease: Observations From a Federated Research Network}},
author = {Leandra Serio and Michele Rossi and Amir Askarinejad and Enrico Tartaglia and Tommaso Bucci and Enrica Marrone and Dinesh K. Kalra and Claudio Ferri and Gregory Y. H. Lip},
journal = {Diabetes, Obesity \& Metabolism},
year = {2026},
month = sep,
doi = {10.1111/dom.71324},
url = {https://doi.org/10.1111/dom.71324},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SGLT2 Inhibitors and Cardiovascular Outcomes in Patients With Fabry Disease: Observations From a Federated Research Network
AU - Leandra Serio
AU - Michele Rossi
AU - Amir Askarinejad
AU - Enrico Tartaglia
AU - Tommaso Bucci
AU - Enrica Marrone
AU - Dinesh K. Kalra
AU - Claudio Ferri
AU - Gregory Y. H. Lip
PY - 2026
DA - 2026/09/08
JO - Diabetes, Obesity & Metabolism
DO - 10.1111/dom.71324
UR - https://doi.org/10.1111/dom.71324
AB - Background and Aim: Fabry disease (FD) is frequently complicated by renal impairment and cardiovascular events; however, evidence on sodium–glucose cotransporter‐2 inhibitors (SGLT2i) in this population is scarce. Accordingly, we assessed the association between SGLT2i exposure and cardiovascular outcomes in adults with FD. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adults with Fabry disease and eGFR ≥ 20 mL/min/1.73 m2, excluding Type 1 diabetes. Patients were stratified by SGLT2 inhibitor exposure. The primary outcome was a composite of all‐cause death, acute myocardial infarction and acute or acute‐on‐chronic heart failure at 2 and 5 years; secondary outcomes included individual components and progression to advanced kidney disease. Patients with prior non‐fatal outcomes were excluded from the respective analyses. Propensity score matching (1:1) and Cox proportional hazards models were used. Sensitivity analyses included alternative follow‐up periods, restriction to Fabry disease diagnosed from 2013 onwards and a stricter Fabry disease definition requiring ≥ 2 diagnoses; subgroup analyses were performed by sex and age. Results: Among 14 940 FD patients, 1028 (6.9%) had recorded exposure to SGLT2 inhibitors (mean age: 65.5 ± 12.0 years; 53.0% male), who were older and had a higher comorbidity burden and worse baseline renal profile than non‐exposed patients. After PSM, 732 patients per group (exposed and non‐exposed patients) were available for analysis. At 2 years, SGLT2i exposure was associated with a lower risk of the composite outcome (HR 0.61; 95% CI 0.38–0.97) and all‐cause death (HR 0.56; 95% CI 0.33–0.95). At 5 years, results were consistent for the composite outcome (HR 0.56; 95% CI 0.39–0.79) and all‐cause death (HR 0.62; 95% CI 0.42–0.93), with reduced myocardial infarction risk (HR 0.53; 95% CI 0.30–0.90). Conclusions: In a large real‐world FD cohort, SGLT2i exposure was associated with lower cardiovascular risk and mortality, supporting further prospective investigation.
SN - 1462-8902
SN - 1463-1326
ER -