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
- 1School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain
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: 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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BibTeX
@article{kajo2026efficacy,
title = {{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}},
author = {Charlie Kajo and Ahmed J. Alaraibi and Osama T. Almutairi and Yaqeen H. Alaraibi and Abdullah Alibrahim and Yousef Kh A. Almutawah and Salem W. S. Alasfar and Mustafa Wasif Ali and Aseel Hajjiri and Mohammad Alqaryuti and Abdullatif Alfehaid and Dana Arekat},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1976876},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1976876/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Charlie Kajo
AU - Ahmed J. Alaraibi
AU - Osama T. Almutairi
AU - Yaqeen H. Alaraibi
AU - Abdullah Alibrahim
AU - Yousef Kh A. Almutawah
AU - Salem W. S. Alasfar
AU - Mustafa Wasif Ali
AU - Aseel Hajjiri
AU - Mohammad Alqaryuti
AU - Abdullatif Alfehaid
AU - Dana Arekat
PY - 2026
DA - 2026/10/21
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1976876
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1976876/full
AB - 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
SN - 2297-055X
ER -