Work

Efficacy of sodium-glucose cotransporter-2 inhibitors on functional mitral regurgitation associated with heart failure: a systematic review and meta-analysis of randomized controlled trials

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Functional mitral regurgitation (FMR) commonly complicates heart failure (HF) and portends a poor prognosis. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve clinical outcomes and induce cardiac reverse remodeling in HF, their specific effect on FMR associated with HF severity remains uncertain. Methods: Five databases were searched from inception to 21 July 2026 for randomized controlled trials (RCTs) evaluating SGLT2i in adult patients with HF and chronic FMR on background guideline-directed medical therapy (GDMT). Primary outcomes were changes from baseline in effective regurgitant orifice area (EROA) and regurgitant volume (RV). Secondary clinical outcomes included HF hospitalization and cardiovascular (CVS) death. Random-effects models were used. Risk of bias was evaluated using the Cochrane RoB 2 tool, and certainty of evidence was assessed using GRADE. Results: = 63.5%, respectively). On leave-one-out sensitivity analyses, statistical significance for both primary valvular outcomes was lost after omitting the EFFORT trial. The certainty of evidence was rated as low. Conclusion: Addition of SGLT2i to GDMT was associated with reductions in FMR severity in pooled analyses; however, these findings were not robust in sensitivity analyses and are limited by low certainty of evidence. The apparent reduction in clinical events requires cautious interpretation due to event sparsity. These results should be considered hypothesis-generating rather than confirmatory, warranting further validation in large-scale, prospective trials. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261462002, PROSPERO CRD420261385207.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2026.1976876