SGLT2 Inhibition as a Novel Therapeutic Strategy in Rheumatic Heart Disease

Rheumatic heart disease (RHD) remains a major cause of cardiovascular morbidity and premature mortality among children and young adults, particularly in low- and middle-income countries. Current management relies on antibiotic prophylaxis and late-stage valve interventions, with no approved pharmacologic therapies targeting the immune-inflammatory and fibrotic processes driving disease progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed for glycemic control, have demonstrated cardiovascular and renal benefits beyond metabolic effects. Their pleiotropic properties - including anti-inflammatory, antifibrotic, antithrombotic, and endothelial-protective actions - align with key mechanisms underlying RHD progression. Preclinical and translational evidence suggests that SGLT2 inhibition can attenuate valvular inflammation, limit fibrosis, and reduce maladaptive remodeling. Emerging clinical data from other valvular diseases indicate potential improvements in hemodynamics and outcomes. This review highlights SGLT2 inhibitors as promising disease-modifying therapies for RHD and underscores the need for dedicated clinical trials to confirm their therapeutic potential.