Key result
SGLT2 inhibitors added to GDMT reduce EROA by ~0.09 cm² vs. placebo.
Why the study?
Patients with moderate-to-severe functional mitral regurgitation often have a poor prognosis despite guideline-directed medical therapy. While SGLT2i are established in heart failure therapy, their impact on FMR severity and outcomes in HFrEF or HFmrEF was unclear.
Does adding SGLT2 inhibitors to guideline-directed medical therapy reduce functional mitral regurgitation severity and improve clinical outcomes in patients with moderate-to-severe FMR and HFrEF or HFmrEF?
Meta-Analysis (n=472)
Does adding SGLT2 inhibitors to guideline-directed medical therapy reduce functional mitral regurgitation severity and improve clinical outcomes in patients with moderate-to-severe FMR and HFrEF or HFmrEF?
In patients with moderate-to-severe functional mitral regurgitation and heart failure, adding SGLT2 inhibitors to GDMT significantly improves mitral regurgitation severity, increases LVEF, and reduces heart failure hospitalizations and cardiovascular mortality.
Supports adding SGLT2 inhibitors to GDMT in HF with functional MR; extends outcome benefits to echocardiographic regurgitation reduction.
Background Functional mitral regurgitation (FMR) is associated with adverse outcomes, including heart failure hospitalizations (HFH) and mortality. Despite guideline-directed medical therapy (GDMT), patients with moderate-to-severe FMR often have poor prognosis. While sodium–glucose cotransporter-2 inhibitors (SGLT2i) are established in GDMT for HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction, their impact on FMR is unclear. We aimed to perform a systematic review and meta-analysis to assess whether adding SGLT2i to GDMT reduces FMR severity and improves outcomes in patients with HFrEF or HFmrEF. Methods PubMed, Scopus, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing SGLT2i versus placebo in patients with moderate-to-severe FMR and HF on GDMT. Echocardiographic outcomes included effective regurgitant orifice area (EROA), regurgitant volume (RVol), and left ventricular ejection fraction (LVEF), while clinical outcomes were cardiovascular (CV) mortality and HFH. Pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results Three RCTs including 472 patients were analyzed, of whom 275 (58%) received SGLT2i. Compared with placebo, SGLT2i was associated with significant reduction in EROA (MD –0.09 cm²; 95% CI –0.15 to –0.02; p=0.008) and RVol (MD –10.89 mL; 95% CI –17.34 to –4.44; p=0.0009), and increase in LVEF (MD +3.59%; 95% CI 1.12–6.06; p=0.004). Clinically, SGLT2i were associated with fewer HFH (RR 0.45; 95% CI 0.28–0.73; p=0.001) and reduced CV mortality (RR 0.26; 95% CI 0.12–0.57; p=0.0008). Conclusion In patients with moderate-to-severe FMR and HF, SGLT2i on top of GDMT was associated with significant improvements in MR severity and LVEF, together with a significant reduction in HFH and CV mortality.
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Stabile et al. (2026) conducted a meta-analysis in Moderate-to-severe functional mitral regurgitation and heart failure (n=472). SGLT-2 inhibitors vs. Placebo on top of guideline-directed medical therapy was evaluated on Effective regurgitant orifice area (EROA) (MD -0.09 cm², 95% CI -0.15 to -0.02, p=0.008). SGLT-2 inhibitors added to GDMT significantly reduced EROA (MD -0.09 cm²; P=0.008), HF hospitalizations (RR 0.45; P=0.001), and CV mortality (RR 0.26; P=0.0008) vs placebo.
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