Impact of SGLT2 inhibitors in patients with Fabry disease

Fabry disease (FD) is a multisystemic disease affecting the heart and the kidneys of affected patients. In addition to FD-specific treatment, patients require concomitant medication for cardio- and nephroprotection. Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) are recommended for patients with heart failure and/or kidney disease, but efficacy data for FD are scarce.

In this multicenter study (n = 8), the effects of SGLT2i therapy after 12 months of treatment in 48 patients (12 females) on FD-specific therapy were examined. Patients were retrospectively analyzed at three time points (before SGLT2i: T_-1; SGLT2i start: T₀; and end of observation: T₊₁). Patients showed advanced cardiac manifestations with a high frequency of left ventricular hypertrophy (LVH) (females: 81.8% and males: 90.0%) at T₀. Males presented with a significantly lower left ventricular ejection fraction LVEF (56 [29-73]% versus 65 [38-78]%; p = 0.0113). There were no treatment-related adverse events or Fabry-associated clinical events (FACEs) between T₀ and T₊₁. Females showed a stable disease course independent of the concomitant treatment with SGLT2i. Males showed an eGFR decrease of 3.7 ml/min/1.73 m² per year (p = 0.0018) before and an ameliorated decrease of 2.7 ml/min/1.73 m² per year (p = 0.0182) after SGLT2i initiation. Importantly, a slight but significant improvement of LVEF by 0.6% per year (p = 0.0319) was observed, which was more prominent in males with a reduced LVEF (< 50%) at baseline.

Treatment with SGLT2i of FD patients was safe and patients presented with stable disease courses. Especially males with reduced LVEF might benefit from SGLT2i treatment.