What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart failure (n=28484). Intervention: SGLT2 inhibitors vs. Placebo or standard therapy. Primary outcome: All-cause mortality (HR 0.86, 95% CI 0.79-0.92, p=<0.001).

What question did this study set out to answer?

This study aims to evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in heart failure patients.

May 13, 2026Frontiers in EndocrinologyOpen Access

Glucose cotransporter-2 inhibitors on mortality and hospitalization in heart failure patients: a comprehensive meta-analysis

Q: What are the key findings of this study?

SGLT2 inhibitors significantly reduced all-cause mortality by 14% (HR 0.86) and heart failure hospitalization by 26% (HR 0.74) in patients with heart failure, regardless of ejection fraction.

Q: What question did this study set out to answer?

This study aims to evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in heart failure patients.

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Key result

SGLT2 inhibitors cut all-cause mortality ~14% and reduce hospitalizations in heart failure regardless of LVEF.

HR 0.86
95% CI 0.79-0.92
P<0.001
n=28,484

Why the study?

Heart failure remains a major challenge with high hospitalization and mortality rates, motivating an evaluation of the impact of SGLT2 inhibitors across ejection fraction and diabetes status.

Does SGLT2 inhibitor therapy reduce all-cause mortality and heart failure hospitalization in patients with heart failure?

Population

28,484 participants across 15 RCTs with heart failure

Comparison

SGLT2 inhibitors vs control

Design

Systematic review and meta-analysis of randomized controlled trials

Authors

XMXiang Mao WLWenhua Liu BHBingqian Hu

Discussion

Member takes

Overview

Supports SGLT2 inhibitor use across all heart failure phenotypes; confirms class-wide mortality and hospitalization benefits.

Key Points

This study aims to evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in heart failure patients.
Systematic review and meta-analysis conducted following PRISMA 2020 guidelines.
Searched electronic databases for randomized controlled trials published from January 2017 to November 2025, including 15 RCTs with 28,484 participants.
Data extraction focused on clinical outcomes, and pooled estimates calculated using a random-effects model.
SGLT2 inhibitors showed a 14% reduction in all-cause mortality (HR = 0.86, 95% CI: 0.79–0.92; p < 0.001).
They led to a 26% reduction in heart failure hospitalization (HR = 0.74, 95% CI: 0.68–0.81; p < 0.001).
Improvements in NT-proBNP levels (mean difference −168.4 pg/mL, 95% CI: −245.6 to −91.2; p < 0.001) and left ventricular systolic function (+3.8% LVEF, 95% CI: +2.4 to +5.2; p < 0.001) were observed.

Study Design

Type

Meta-Analysis (n=28,484)

Structured PICO

Does SGLT2 inhibitor therapy reduce all-cause mortality and heart failure hospitalization in patients with heart failure?

Population

15 RCTs pooling 28,484 adult patients with heart failure (HFrEF and HFpEF), irrespective of diabetes status.

Intervention

SGLT2 inhibitors as a class (including empagliflozin, dapagliflozin, sotagliflozin, luseogliflozin) added to background heart failure therapy.

Comparator

Placebo or standard therapy (e.g., standard diuretic, ARB) added to background heart failure therapy.

Outcome

All-cause mortality and heart failure hospitalization.hard clinical

Main Result

Effect estimate: HR 0.86 (95% CI 0.79-0.92)

p-value: p=<0.001

SGLT2 inhibitors significantly reduce all-cause mortality and heart failure hospitalizations while improving cardiac function and biomarkers across all heart failure phenotypes, confirming a class effect.

Limitations

Inclusion of small mechanistic studies with a limited number of participants introduces variability.
Limited granularity of data, preventing analysis of outcomes by sex and renal function.
Need to analyze the relationship between SGLT2 inhibitor therapy and other treatments, sequence of therapy, and timing of initiation.
Moderate heterogeneity for hospitalization outcomes due to differences in study populations (HFpEF vs. HFrEF) and length of follow-up
Lack of blinding in some smaller mechanistic or early-phase included trials, potentially introducing performance bias
Missing data and small sample sizes in some included studies

Cite This Study

Mao et al. (2026) conducted a meta-analysis in Heart failure (n=28,484). SGLT2 inhibitors vs. Placebo or standard therapy was evaluated on All-cause mortality (HR 0.86, 95% CI 0.79-0.92, p=<0.001). SGLT2 inhibitors significantly reduced all-cause mortality by 14% (HR 0.86) and heart failure hospitalization by 26% (HR 0.74) in patients with heart failure, regardless of ejection fraction.

synapsesocial.com/papers/6a158ec3d64fa333899fced8 https://doi.org/10.3389/fendo.2026.1758519

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May 13, 2026Frontiers in EndocrinologyOpen Access

Glucose cotransporter-2 inhibitors on mortality and hospitalization in heart failure patients: a comprehensive meta-analysis

View Full Paper

Ask AI

Bookmark

Key result

SGLT2 inhibitors cut all-cause mortality ~14% and reduce hospitalizations in heart failure regardless of LVEF.

HR 0.86
95% CI 0.79-0.92
P<0.001
n=28,484

Why the study?

Heart failure remains a major challenge with high hospitalization and mortality rates, motivating an evaluation of the impact of SGLT2 inhibitors across ejection fraction and diabetes status.

Does SGLT2 inhibitor therapy reduce all-cause mortality and heart failure hospitalization in patients with heart failure?

Population

28,484 participants across 15 RCTs with heart failure

Comparison

SGLT2 inhibitors vs control

Design

Systematic review and meta-analysis of randomized controlled trials

Authors

XMXiang Mao WLWenhua Liu BHBingqian Hu

Discussion

Member takes

Overview

Supports SGLT2 inhibitor use across all heart failure phenotypes; confirms class-wide mortality and hospitalization benefits.

Key Points

This study aims to evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in heart failure patients.
Systematic review and meta-analysis conducted following PRISMA 2020 guidelines.
Searched electronic databases for randomized controlled trials published from January 2017 to November 2025, including 15 RCTs with 28,484 participants.
Data extraction focused on clinical outcomes, and pooled estimates calculated using a random-effects model.
SGLT2 inhibitors showed a 14% reduction in all-cause mortality (HR = 0.86, 95% CI: 0.79–0.92; p < 0.001).
They led to a 26% reduction in heart failure hospitalization (HR = 0.74, 95% CI: 0.68–0.81; p < 0.001).
Improvements in NT-proBNP levels (mean difference −168.4 pg/mL, 95% CI: −245.6 to −91.2; p < 0.001) and left ventricular systolic function (+3.8% LVEF, 95% CI: +2.4 to +5.2; p < 0.001) were observed.

Study Design

Type

Meta-Analysis (n=28,484)

Structured PICO

Does SGLT2 inhibitor therapy reduce all-cause mortality and heart failure hospitalization in patients with heart failure?

Population

15 RCTs pooling 28,484 adult patients with heart failure (HFrEF and HFpEF), irrespective of diabetes status.

Intervention

SGLT2 inhibitors as a class (including empagliflozin, dapagliflozin, sotagliflozin, luseogliflozin) added to background heart failure therapy.

Comparator

Placebo or standard therapy (e.g., standard diuretic, ARB) added to background heart failure therapy.

Outcome

All-cause mortality and heart failure hospitalization.hard clinical

Main Result

Effect estimate: HR 0.86 (95% CI 0.79-0.92)

p-value: p=<0.001

Limitations

Inclusion of small mechanistic studies with a limited number of participants introduces variability.
Limited granularity of data, preventing analysis of outcomes by sex and renal function.
Need to analyze the relationship between SGLT2 inhibitor therapy and other treatments, sequence of therapy, and timing of initiation.
Moderate heterogeneity for hospitalization outcomes due to differences in study populations (HFpEF vs. HFrEF) and length of follow-up
Lack of blinding in some smaller mechanistic or early-phase included trials, potentially introducing performance bias
Missing data and small sample sizes in some included studies

Cite This Study

synapsesocial.com/papers/6a158ec3d64fa333899fced8 https://doi.org/10.3389/fendo.2026.1758519

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

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