SGLT2 inhibitors show promise for heart health in Fabry: Study
Analysis finds treatment especially beneficial for men with reduced heart function
Written by |
A class of medications commonly used to treat heart and kidney disease, called sodium-glucose co-transporter 2 (SGLT2) inhibitors, appears to be safe in adults with Fabry disease and may offer some benefits for heart health, a study suggested.
An analysis of outcomes in 48 patients treated with an SGLT2 inhibitor showed stable disease in most cases and improvements in heart function, especially among men with reduced heart function at the start of treatment.
SGLT2 inhibitors “may be a useful concomitant medication,” particularly for men with reduced heart function, the researchers wrote.
The study, “Impact of SGLT2 inhibitors in patients with Fabry disease,” was published in Clinical Research in Cardiology.
Fabry disease occurs when mutations impair the function of the enzyme alpha-galactosidase A (alpha-Gal A), leading to the abnormal buildup of certain fatty molecules within cells. Over time, this leads to progressive damage to multiple organs, including the heart, kidneys, and nervous system, causing a range of Fabry symptoms.
Heart, kidney protection
Two classes of therapies are approved for Fabry treatment. Enzyme replacement therapy (ERT) works by regularly supplying a functional version of the missing alpha-Gal A enzyme, while chaperone therapy helps stabilize the existing enzyme to improve its function. Both are expected to ease symptoms and slow disease progression.
In addition to Fabry-specific treatments, people with Fabry are often prescribed medications to protect the heart and kidneys when these organs are affected.
SGLT2 inhibitors are commonly used to help protect heart and kidney function in people with heart failure and/or kidney disease. “However, so far, SGLT2 inhibitor efficacy data in patients with [Fabry disease] are scarce,” the researchers wrote.
To address this gap, they retrospectively analyzed data from 48 adults with Fabry disease treated with SGLT2 inhibitors across eight centers in Germany, Austria, and Switzerland. Twelve of them were women, with a median age of 60, and 36 were men, with a median age of 58.
Participants were assessed for changes in heart and kidney function at three time points: one year before starting an SGLT2 inhibitor, at the start of treatment, and again about one year later. All had been on stable ERT or chaperone therapy for at least six months before the first assessment.
At the start of treatment, both women and men showed advanced Fabry disease, with heart and kidney involvement.
Thickening of the heart’s left ventricle — the chamber that pumps blood to the body — known as left ventricular hypertrophy (LVH), was common in both groups, affecting 81.8% of women and 90% of men. However, men had poorer heart function, with a median left ventricular ejection fraction (LVEF) — a measure of how well the left ventricle pumps blood — of 56%, compared with 65% in women. All patients had elevated levels of NT-proBNP and troponin T, two markers of heart stress and damage.
Men and women showed similar kidney function. However, men had higher levels of albumin in their urine (albuminuria), a sign of kidney damage, indicating more severe kidney involvement.
SGLT2 inhibitors were prescribed for heart (40%), kidney (27%), or combined heart and kidney (33%) involvement. Most participants (69%) received dapagliflozin (sold as Farxiga and generics), while the remaining 31% received empagliflozin (sold under the brand name Jardiance, among others).
Overall, treatment with SGLT2 inhibitors was found to be safe. During about one year of follow-up, researchers reported no major clinical events involving the heart, kidneys, or brain, and no clinically relevant side effects.
Women generally showed a stable disease course, with no significant changes in heart structure, heart or kidney function, or albumin and troponin T levels after starting treatment. NT-proBNP levels, which had increased significantly in the year before treatment, remained stable during SGLT2 inhibitor therapy.
In men, kidney function had been declining before treatment. It continued to decline after starting SGLT2 inhibitors, but at a slightly slower rate, suggesting a possible stabilizing effect. The clearest benefit in men was seen in heart function, with a significant increase in LVEF of 0.6% per year after starting treatment. This improvement was more pronounced in men who had reduced ejection fraction at the start of treatment, in whom LVEF increased by about 0.8% per year.
Levels of NT-proBNP and troponin T decreased over time in about half of the men who had elevated levels at the start of treatment.
“Treatment with [SGLT2 inhibitors] in [Fabry disease] patients under ERT or chaperone therapy was safe,” the researchers concluded, noting that “SGLT2 inhibition seems to be a useful concomitant medication” in people with Fabry-related heart and kidney disease. They added that these findings “should be clarified in future controlled prospective studies.”
