Clinical outcomes of GLP-1 receptor agonists VS placebo among patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis

Q: What are the key findings of this study?

GLP-1 receptor agonists reduced adjudicated heart failure events compared to placebo in patients with HFpEF.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart failure with preserved ejection fraction (HFpEF) (n=1463). Intervention: GLP-1 receptor agonists (Semaglutide) vs. Placebo. Primary outcome: Adjudicated heart failure events (hospitalization or urgent visit to emergency department for heart failure) (OR 0.32, 95% CI 0.15-0.67, p=<0.05).

Q: What does this research mean for the field?

GLP-1 receptor agonists significantly reduce adjudicated heart failure events and improve functional status in patients with HFpEF, though they do not significantly reduce all-cause or cardiovascular mortality. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

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

To evaluate the clinical efficacy and safety outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) compared with placebo in patients with heart failure with preserved ejection fraction (HFpEF).

Edward Davis; Leonardo Alexander; Nikolaus Tobian; Fernando Alonzo Theja; Ardeno Kristianto; Linawati Hananta

doi:10.1186/s43044-026-00793-w

November 14, 2026The Egyptian Heart JournalOpen Access

Clinical outcomes of GLP-1 receptor agonists VS placebo among patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis

View Full Paper

Ask AI

Bookmark

Share

Key result

GLP-1 receptor agonists reduce heart failure events ~68% vs. placebo in HFpEF.

OR 0.32
95% CI 0.15-0.67
P<0.05
n=1,463

Why the study?

HFpEF involves complex pathophysiology worsened by comorbidities like obesity and diabetes, and currently has limited treatment options. This study evaluated the impact of GLP-1 RA on clinical outcomes in HFpEF.

Do GLP-1 receptor agonists reduce adjudicated heart failure events and mortality or improve functional capacity and quality of life compared to placebo in patients with heart failure with preserved ejection fraction (HFpEF)?

Key Points

To evaluate the clinical efficacy and safety outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) compared with placebo in patients with heart failure with preserved ejection fraction (HFpEF).
Systematic review and meta-analysis of 3 studies encompassing 1463 patients identified across 5 databases (Sage, ProQuest, ScienceDirect, PubMed, and EBSCO) up to November 2024.
Quantitative synthesis performed using a random effects model, reporting pooled odds ratios (OR) with 95% confidence intervals (CI) and heterogeneity assessed by the I2 statistic.
GLP-1 RA use significantly reduced adjudicated heart failure events compared to placebo (pooled OR 0.32, 95% CI: 0.15–0.67, p < 0.05, I2 = 5%).
No statistically significant difference was observed for all-cause mortality (pooled OR 0.63, 95% CI: 0.27–1.48, p = 0.29, I2 = 0%) or cardiovascular mortality (pooled OR 0.27, 95% CI: 0.04–1.66, p = 0.16, I2 = 0%).
Treatment was associated with reductions in NT-proBNP levels and consistent improvements in 6-minute walk test distances and Kansas City Cardiomyopathy Questionnaire clinical summary scores.

Study Design

Type

Meta-Analysis (n=1,463)

Structured PICO

Do GLP-1 receptor agonists reduce adjudicated heart failure events and mortality or improve functional capacity and quality of life compared to placebo in patients with heart failure with preserved ejection fraction (HFpEF)?

P

Population

1,463 patients across 3 studies (2 RCTs and 1 retrospective cohort) with heart failure with preserved ejection fraction (HFpEF) and obesity (with or without type 2 diabetes), mean/median age 69 years, followed for 52 weeks.

I

Intervention

Glucagon-like peptide-1 receptor agonists (specifically semaglutide, escalated to a maintenance dose of 2.4 mg once weekly) for 52 weeks

C

Comparator

Placebo

O

Outcome

Adjudicated heart failure events (composite of hospitalization or urgent visit to emergency department for heart failure) at 52 weekscomposite

Main Result

Odds Ratio: 0.32 (95% CI 0.15–0.67)

p-value: p=<0.05

In patients with obesity-related HFpEF, GLP-1 receptor agonist therapy (semaglutide) significantly reduces adjudicated heart failure events and improves functional capacity and quality of life over 52 weeks, though larger and longer trials are needed to assess mortality.

Limitations

Restricted pool of literature comprising only three eligible studies with different study designs (two RCTs and one retrospective cohort)
Relatively small total sample size (1,463 patients) limiting statistical power to detect mortality differences
Follow-up duration limited to 52 weeks across all included studies, which may be insufficient to capture long-term mortality outcomes
Difficulty distinguishing whether functional and quality of life improvements result from direct cardioprotective effects or are secondary to weight reduction
Quantitative synthesis based on only three eligible studies with different study designs (two RCTs and one retrospective cohort)
Small total sample size of 1,463 patients constraining statistical power for mortality endpoints
Follow-up duration across all included studies limited to 52 weeks, insufficient for long-term mortality outcomes
Unclear extent to which clinical improvements reflect direct cardioprotective effects versus weight reduction

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Supports GLP-1 RA use to reduce HF events in HFpEF; extends STEP-HFpEF data with pooled analysis of 3 trials.

Abstract

Background Heart failure with preserved ejection fraction (HFpEF) is a complex form of heart failure which is marked by impaired diastolic function. It has complex pathophysiology involving systemic inflammation, myocardial fibrosis and arterial stiffness. The existence of other comorbidities namely obesity and diabetes further worsens these processes. Currently there is limited treatment option for HFpEF. Methods Systematic search from 5 databases was conducted to identify studies that evaluated the impacts of glucagon-like peptide-1 receptor agonist (GLP-1 RA) on the clinical outcomes of HFpEF. Quantitative analysis was performed using random effect model were performed on clinical outcomes. Results are presented as odds ratio (OR) along with its 95% confidence interval. Results 3 Studies involving 1463 patients were included. GLP-1 RA reduced NT-pro Brain Natriuretic Peptide (NT-pro BNP) levels and enhanced 6-minute walking test, Kansas City Cardiomyopathy Questionnaire clinical summary score. Significant reduction in adjudicated heart failure event was observed (OR 0.32, 95% CI: 0.15–0.67, p < 0.05, I 2 = 5%). No significant difference in all-cause mortality (OR 0.63, 95% CI: 0.27–1.48, p = 0.29, I2 = 0%) and cardiovascular mortality (OR 0.27, 95% CI: 0.04–1.66, p = 0.16, I2 = 0%) were observed. Conclusion GLP-1 RA was effective in improving quality of life parameters and lowered the risk of cardiovascular events of HFpEF patients; however it did not significantly reduce mortality in those who suffered from HFpEF.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Davis et al. (2026) conducted a meta-analysis in Heart failure with preserved ejection fraction (HFpEF) (n=1,463). GLP-1 receptor agonists (Semaglutide) vs. Placebo was evaluated on Adjudicated heart failure events (hospitalization or urgent visit to emergency department for heart failure) (OR 0.32, 95% CI 0.15-0.67, p=<0.05). GLP-1 receptor agonists reduced adjudicated heart failure events compared to placebo in patients with HFpEF.

synapsesocial.com/papers/6af9ebcdd393cbc380a05026 https://doi.org/10.1186/s43044-026-00793-w

View Full Paper

Ask AI

Bookmark

Share

Clinical outcomes of GLP-1 receptor agonists VS placebo among patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Clinical outcomes of GLP-1 receptor agonists VS placebo among patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading