SGLT2 Inhibitors Emerge as Promising Disease-Modifying Therapy for Rheumatic Heart Disease: Review
France: Rheumatic heart disease (RHD) continues to be a major cause of cardiovascular illness and premature death worldwide, particularly among children and young adults in low- and middle-income countries. Despite affecting millions of people, treatment options remain limited, with current care largely focused on preventing recurrent streptococcal infections and managing advanced valvular damage.
A new state-of-the-art review published in JACC: Asia suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors could emerge as a novel disease-modifying therapy for RHD. The review was led by Olivier Morel, Department of Cardiology, University Hospital of Strasbourg, France, and colleagues.
Rheumatic heart disease results from immune-mediated damage following Group A streptococcal infection and is characterized by chronic inflammation, fibrosis, and progressive valve damage, primarily involving the mitral and aortic valves. Current treatment focuses on infection prevention and valve intervention, with no approved therapies targeting the underlying disease processes.
SGLT2 inhibitors, originally developed for diabetes, have shown substantial cardiovascular and renal benefits in conditions such as heart failure and chronic kidney disease. Growing evidence suggests their effects extend beyond glucose control, making them potential candidates for disease modification in RHD.
Key Takeaways:
- SGLT2 inhibitors exhibit anti-inflammatory, antifibrotic, endothelial-protective, and antithrombotic effects that target key mechanisms involved in rheumatic heart disease progression.
- Experimental and translational studies suggest that SGLT2 inhibition may reduce valvular inflammation and limit fibrotic remodeling.
- SGLT2 inhibitors may help slow structural damage to heart valves affected by rheumatic heart disease.
- Evidence from other valvular heart diseases indicates that SGLT2 inhibitors may improve cardiac function, hemodynamics, and clinical outcomes.
- The biological and clinical evidence supports the potential role of SGLT2 inhibitors as disease-modifying therapy for rheumatic heart disease.
- SGLT2 inhibitors are administered orally, have a favorable safety profile, and are relatively inexpensive.
- These characteristics make SGLT2 inhibitors attractive candidates for large-scale implementation in low- and middle-income countries, where the burden of rheumatic heart disease is greatest.
- The review highlights the potential of SGLT2 inhibitors to address unmet therapeutic needs and improve access to innovative cardiovascular treatments in resource-limited settings.
However, the authors cautioned that direct evidence in patients with rheumatic heart disease remains limited. While mechanistic data and early clinical observations are encouraging, randomized controlled trials specifically evaluating SGLT2 inhibitors in RHD are currently lacking.
The researchers concluded that SGLT2 inhibitors represent a promising therapeutic strategy capable of targeting the inflammatory, endothelial, and fibrotic pathways that drive RHD progression. They emphasized the urgent need for dedicated clinical trials to determine whether these agents can improve outcomes and alter the natural history of this neglected disease. If confirmed, SGLT2 inhibitors could mark a significant advance in the management of rheumatic heart disease, particularly in regions where its burden remains greatest.
Reference:
Morel, O., Mai, A. T., Zühlke, L., Jouven, X., Marchandot, B., Pressman, G., Patton-Bolman, C., Roffi, M., & Pibarot, P. (2026). SGLT2 Inhibition as a Novel Therapeutic Strategy in Rheumatic Heart Disease. JACC: Asia, 6(6), 839-847. https://doi.org/10.1016/j.jacasi.2026.03.034
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