Key result
SGLT2 inhibitors may attenuate inflammation and fibrosis in rheumatic heart disease based on preclinical evidence.
Why the study?
No pharmacological intervention modifies valvular disease progression in established RHD, prompting evaluation of the mechanistic plausibility of SGLT2 inhibitors.
This hypothesis-generating review outlines the mechanistic plausibility and translational pathway for investigating SGLT2 inhibitors as a potential disease-modifying therapy to halt valvular progression in rheumatic heart disease.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for SGLT2 inhibitors in rheumatic heart disease; prospective trials needed before considering disease modification.
Rheumatic heart disease (RHD) remains the leading cause of acquired valvular heart disease in low- and middle-income countries, affecting an estimated 40 million individuals and disproportionately affecting children and young adults in endemic regions. No pharmacological intervention has been shown to modify valvular disease progression in established RHD. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardioprotective effects across multiple cardiovascular conditions, prompting interest in their potential applicability to RHD. This hypothesis-generating review synthesizes current evidence on the molecular and cellular pathology of RHD and evaluates the mechanistic plausibility of SGLT2 inhibitor effects in this context. Evidence derived largely from non-rheumatic valve disease and experimental models suggests that SGLT2 inhibitors may attenuate oxidative stress, inflammatory cytokine signaling, transforming growth factor-β-driven fibrosis, and mitochondrial dysfunction; processes implicated in valvular remodeling. Mechanotransduction cascades and osteogenic calcification pathways, characterized primarily in calcific aortic valve disease, are biologically plausible but remain uncharacterized in RHD tissue. Whether these mechanisms are operative within the postinflammatory, immune-mediated rheumatic valve environment remains uncertain and represents an important avenue for future research. Validation of SGLT2 expression in rheumatic valve tissue, mechanistic testing in etiologically relevant models, and early-phase clinical trials tailored to endemic health system realities are essential prerequisites before any therapeutic claims can be advanced. This review outlines the translational pathway needed to determine whether this hypothesis warrants clinical development.
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Anh et al. (2026) conducted a review in Rheumatic Heart Disease. SGLT2 inhibitors was evaluated. Evidence derived largely from non-rheumatic valve disease and experimental models suggests that SGLT2 inhibitors may attenuate oxidative stress, inflammatory signaling, and fibrosis in rheumatic heart disease.
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