July 4, 2025Frontiers in Cardiovascular MedicineOpen Access

Investigating the effect of SGLT2 inhibitors on cardiovascular related health status in HFmrEF and HFpEF: systematic review and meta analysis

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Why the study?

The impact of SGLT2 inhibitors on quality of life in patients with HFmrEF and HFpEF remains underexplored.

Do SGLT2 inhibitors improve quality of life and functional capacity in patients with HFmrEF and HFpEF?

Structured PICO

Do SGLT2 inhibitors improve quality of life and functional capacity in patients with HFmrEF and HFpEF?

Population

Patients with heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) from up to 7 RCTs

Intervention

Sodium-glucose co-transporter 2 inhibitors (SGLT2i)

Comparator

Placebo

Outcome

Changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score and 6 Minute Walk Test Distance (6MWTD)patient reported

SGLT2 inhibitors significantly improve patient-reported health status and functional capacity in patients with mildly reduced and preserved ejection fraction heart failure.

Implication

Supports SGLT2i incorporation for QoL gains in HFmrEF/HFpEF; extends RCT meta-analytic confirmation of patient-centered benefits.

Abstract

Background and aims Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as an integral component of heart failure management, with evidence supporting their benefits across a broad spectrum of ejection fractions. However, their impact on quality of life (QoL) in patients with heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains underexplored. This systematic review and meta-analysis aim to evaluate the effects of SGLT2i on QoL compared to standard therapy in these patient populations. Methods A systematic search of PubMed, Cochrane, and EMBASE databases was conducted for randomized controlled trials (RCTs) published in English that assessed the clinical outcomes of SGLT2i in HFpEF and HFmrEF up to January 23, 2024. Two independent reviewers evaluated the risk of bias for eligible studies. A random-effects model was used for meta-analysis. The primary outcomes of interest were changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score and 6 Minute Walk Test Distance (6MWTD). Findings A total of 7 RCTs comparing KCCQ score in HFpEF and HFmrEF in participants receiving SGLT2i vs. placebo, and 3 RCTs comparing 6MWTD in HFpEF and HFmrEF in participants receiving SGLT2i vs. placebo were included in the systematic review. Overall SGLT2i was associated with an increase in KCCQ-TSS score (MD = 2.28, 95% CI 1.94–2.63, I 2 = 0%) and 6MWTD (MD = 13.52, 95% CI 1.70–25.34, I 2 = 62%). Interpretation These findings suggest that SGLT2i not only confer cardiovascular benefits but also enhance patient-reported health status, reinforcing their role as a valuable adjunct to standard heart failure therapy in HFmrEF and HFpEF.