Key result
SGLT2 inhibitors added to GDMT reduce effective regurgitant orifice area by ~0.09 cm² in functional MR.
Why the study?
While SGLT2i improve clinical outcomes and induce cardiac reverse remodeling in heart failure, their specific effect on functional mitral regurgitation severity remained uncertain.
Does adding an SGLT2 inhibitor to guideline-directed medical therapy reduce effective regurgitant orifice area and regurgitant volume in adult patients with heart failure and chronic functional mitral regurgitation?
Meta-Analysis (n=455)
Mixed (1 double-blind placebo-controlled trial, 2 open-label trials with blinded outcome assessment)
Included 3 RCTs
Yes
Does adding an SGLT2 inhibitor to guideline-directed medical therapy reduce effective regurgitant orifice area and regurgitant volume in adult patients with heart failure and chronic functional mitral regurgitation?
Adding SGLT2 inhibitors to GDMT is associated with reductions in functional mitral regurgitation severity (EROA and RV) in heart failure patients, though findings are hypothesis-generating due to high heterogeneity and sensitivity to single-trial omission.
SGLT2 inhibitors may modestly lessen FMR severity on GDMT; low-certainty meta-analysis of 3 RCTs leaves open need for robust confirmation.
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 Three RCTs involving 455patients were included. SGLT2i therapy was associated with a statistically significant reduction in EROA (MD −0.086 cm 2 , 95% CI −0.150 to −0.022) and RV (MD −10.87 mL, 95% CI −17.32 to −4.43), but substantial heterogeneity was observed (I 2 = 72.5% and I 2 = 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
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Kajo et al. (2026) conducted a meta-analysis in Heart failure and concomitant chronic functional mitral regurgitation (n=455). SGLT2 inhibitors (Dapagliflozin or Ertugliflozin) plus GDMT vs. Placebo plus GDMT or GDMT alone was evaluated on Change from baseline in effective regurgitant orifice area (EROA, cm²) (MD -0.086 cm², 95% CI -0.150 to -0.022, p=0.0089). SGLT2 inhibitors added to GDMT significantly reduced effective regurgitant orifice area (MD -0.086 cm², p=0.0089) and regurgitant volume (MD -10.87 mL, p=0.0009) in patients with heart failure and FMR.
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