SGLT2 inhibitors in fabry disease: a real-world evaluation of cardiac and renal biomarker response
I Arosi, R Oatham, A Moore, A Ochoa-Ferraro, R Steeds, T Geberhiwot, N LewisAbstract
Background
Fabry disease is a rare, progressive lysosomal storage disorder frequently complicated by cardiac involvement, including left-ventricular hypertrophy, arrhythmias, and heart failure. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated benefit across multiple heart failure phenotypes, but evidence in Fabry disease remains limited.
Purpose
To evaluate cardiac and renal biomarker trends in patients with Fabry disease treated with SGLT2i and to determine whether these agents may have a therapeutic role in this population.
Methods
A retrospective analysis was performed using multiple datasets. Patients were recruited from two UK specialist centres. Patients receiving SGLT2i for ≥1 year with complete biomarker data were included. Serial NT-proBNP, troponin, albumin–creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) values were compared between baseline and 1-year follow-up. Additional clinical outcomes, including mortality and treatment discontinuation, were recorded.
Results
Eighteen patients met inclusion criteria; all were receiving enzyme replacement therapy at SGLT2i initiation. The mean interval between baseline and follow-up assessments was 382 days. NT-proBNP showed a small, non-significant improvement (1795 → 1721 pg/mL). Troponin values demonstrated a similarly modest, non-significant reduction (187 → 181 ng/L). eGFR declined significantly over follow-up (65 → 59 mL/min/1.73 m²; p=0.05), consistent with the early haemodynamic dip observed with SGLT2i or with Fabry-related renal progression. Mean ACR decreased from 46 to 38 mg/mmol, though this change was not statistically significant. Two deaths occurred during follow-up, and one patient discontinued therapy due to intolerance.
Conclusions
In this real-world Fabry cohort, SGLT2i therapy was associated with favourable, though non-significant, trends in NT-proBNP, troponin, and ACR. The observed decline in eGFR may reflect the early haemodynamic effect characteristic of SGLT2i use, and the concurrent improvement in ACR suggests no overt worsening of renal disease during the treatment period. These findings support the potential utility of SGLT2i in Fabry-related cardiac disease; however, larger prospective studies are required to confirm clinical efficacy and clarify renal safety in this population.