Sodium-Glucose Cotransporter 2 Inhibitors in Valvular Heart Disease: Cardiovascular Benefit, Valve-Specific Effects, and Evidence Gaps-A Structured Narrative Review
Abstract
Background/Objectives: Native valvular heart disease (VHD) lacks established lesion-modifying pharmacotherapy. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) improve heart-failure and cardiorenal outcomes, but their relevance to VHD differs by phenotype and treatment setting. Methods: MEDLINE/PubMed, Scopus, Web of Science Core Collection and Cochrane CENTRAL were searched from inception to 27 July 2026, together with trial registries, conference proceedings and reference lists. Evidence was synthesized by clinical setting, study design and mechanistic proximity to valve tissue. Results: Functional/secondary mitral regurgitation (MR) currently provides the most convincing valve-related signal: EFFORT and DEFORM showed concordant reductions in MR severity with favorable remodeling surrogates, consistent with HF-directed unloading rather than a primary leaflet effect. DapaTAVI provides the strongest hard-outcome evidence after the mechanical correction of aortic stenosis, reducing the 1-year death/worsening-HF composite in selected high-risk patients. In 28,940 HF patients from the SHEBAHEART registry, SGLT2i use was associated with reduced death/HF hospitalization and a 28% lower adjusted risk of tricuspid-regurgitation progression, but these data remain observational. Native aortic-stenosis progression is supported only by target-trial emulation, and no dedicated clinical evidence exists for native aortic regurgitation. Conclusions: SGLT2is should be integrated into…
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