GLP-1 Receptor Agonists in Heart Failure: A Systematic Review and Meta-analysis with Phenotype-Specific Effects and Dual Analytical Frameworks.

Yuan Y, Chen C, Li X, Guo J, Liu Q, Lin Y, Sun L, Fan G

Drugs26 Sept 2026

PMID42791433DOI10.1007/s40265-026-02380-4PepBankPUB-42791433

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study16

2 results from studies that gave the peptide. 2 results from people.

01HumanSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, semaglutide showed benefit on hospitalization for heart failure, mainly in overweight or obese patients.
In plain wordsIn people with preserved-ejection-fraction heart failure, semaglutide lowered hospital stays for heart failure, mostly in people with overweight or obesity.
Peptide
Semaglutide
Outcome
DecreaseSemaglutide effect on hospitalization for HF in HFpEF
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide showed benefits in HHF and the composite of cardiovascular death or worsening HF events predominantly among overweight or obese patients with HFpEF.
1 context sentence(design, population, supporting numbers)
Summary · context
A prespecified targeted analysis was conducted to specifically assess the efficacy of semaglutide.
Report a problemFND-4279143315
02HumanSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, semaglutide showed benefit on the composite of cardiovascular death or worsening heart failure, mainly in overweight or obese patients.
In plain wordsIn people with preserved-ejection-fraction heart failure, semaglutide lowered heart-related death or worsening heart failure, mostly in people with overweight or obesity.
Peptide
Semaglutide
Outcome
DecreaseSemaglutide effect on CV death or worsening HF in HFpEF
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide showed benefits in HHF and the composite of cardiovascular death or worsening HF events predominantly among overweight or obese patients with HFpEF.
1 context sentence(design, population, supporting numbers)
Summary · context
A prespecified targeted analysis was conducted to specifically assess the efficacy of semaglutide.
Report a problemFND-4279143316

Studies that did not test the peptide alone14

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

03HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, pooled GLP-1 receptor agonists reduced major adverse cardiovascular events (HR 0.79).
In plain wordsIn people with preserved-ejection-fraction heart failure, pooled GLP-1 drugs lowered major heart and blood vessel events.
Peptide
Semaglutide
Outcome
DecreaseMACE in HFpEF
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.79 ratio
HFpEF, MACE
Source sentences
Summary
In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143301
04HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with reduced ejection fraction, pooled GLP-1 receptor agonists did not significantly reduce major adverse cardiovascular events.
In plain wordsIn people with reduced-ejection-fraction heart failure, pooled GLP-1 drugs did not clearly lower major heart and blood vessel events.
Peptide
Semaglutide
Outcome
No significant changeMACE in HFrEF
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143308
05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In heart failure subgroups of cardiovascular outcome trials, pooled GLP-1 receptor agonists reduced major adverse cardiovascular events (HR 0.82).
In plain wordsIn people with heart failure from large cardiovascular trials, pooled GLP-1 drugs lowered major heart and blood vessel events.
Peptide
Semaglutide
Outcome
DecreaseMACE in HF subgroups from CVOTs
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.82 ratio
CVOT HF subgroups, MACE
Source sentences
Summary
Trial-level analyses showed that cardiovascular benefits were primarily observed in HF subgroups from CVOTs, including reductions in MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001), cardiovascular death (HR 0.88; 95% CI 0.77-1.00; p = 0.05) and myocardial infarction (MI)/non-fatal MI (HR 0.84; 95% CI 0.70-1.00; p = 0.046).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143310
06HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, pooled GLP-1 receptor agonists reduced hospitalization for heart failure (HR 0.48).
In plain wordsIn people with preserved-ejection-fraction heart failure, pooled GLP-1 drugs lowered hospital stays for heart failure.
Peptide
Semaglutide
Outcome
DecreaseHospitalization for HF in HFpEF
Study
n: not reported in source
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.48 ratio
HFpEF, HHF
Source sentences
Summary
In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143302
07HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, pooled GLP-1 receptor agonists reduced the composite of cardiovascular death or worsening heart failure (HR 0.57).
In plain wordsIn people with preserved-ejection-fraction heart failure, pooled GLP-1 drugs lowered heart-related death or worsening heart failure.
Peptide
Semaglutide
Outcome
DecreaseCV death or worsening HF in HFpEF
Study
n: not reported in source
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.57 ratio
HFpEF, composite
Source sentences
Summary
In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143303
08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, pooled GLP-1 receptor agonists reduced all-cause mortality (HR 0.75).
In plain wordsIn people with preserved-ejection-fraction heart failure, pooled GLP-1 drugs lowered deaths from any cause.
Peptide
Semaglutide
Outcome
DecreaseAll-cause mortality in HFpEF
Study
n: not reported in source
Analysis
Secondary
Outcome group
Mortality · Cardiovascular
Measurements
HR
0.75 ratio
HFpEF, all-cause mortality
Source sentences
Summary
In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143304
09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with reduced ejection fraction, pooled GLP-1 receptor agonists did not significantly reduce hospitalization for heart failure.
In plain wordsIn people with reduced-ejection-fraction heart failure, pooled GLP-1 drugs did not clearly lower hospital stays for heart failure.
Peptide
Semaglutide
Outcome
No significant changeHospitalization for HF in HFrEF
Study
n: not reported in source
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143305
10HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with reduced ejection fraction, pooled GLP-1 receptor agonists did not significantly reduce the composite of cardiovascular death or worsening heart failure.
In plain wordsIn people with reduced-ejection-fraction heart failure, pooled GLP-1 drugs did not clearly lower heart-related death or worsening heart failure.
Peptide
Semaglutide
Outcome
No significant changeCV death or worsening HF in HFrEF
Study
n: not reported in source
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143306
11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with reduced ejection fraction, pooled GLP-1 receptor agonists did not significantly reduce all-cause mortality.
In plain wordsIn people with reduced-ejection-fraction heart failure, pooled GLP-1 drugs did not clearly lower deaths from any cause.
Peptide
Semaglutide
Outcome
No significant changeAll-cause mortality in HFrEF
Study
n: not reported in source
Analysis
Secondary
Outcome group
Mortality · Cardiovascular
Source sentences
Summary
In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143307
12HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In heart failure subgroups of cardiovascular outcome trials, pooled GLP-1 receptor agonists reduced cardiovascular death (HR 0.88).
In plain wordsIn people with heart failure from large cardiovascular trials, pooled GLP-1 drugs lowered heart-related death.
Peptide
Semaglutide
Outcome
DecreaseCardiovascular death in HF subgroups from CVOTs
Study
n: not reported in source
Analysis
Secondary
Outcome group
Mortality · Cardiovascular
Measurements
HR
0.88 ratio
CVOT HF subgroups, cardiovascular death
Source sentences
Summary
Trial-level analyses showed that cardiovascular benefits were primarily observed in HF subgroups from CVOTs, including reductions in MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001), cardiovascular death (HR 0.88; 95% CI 0.77-1.00; p = 0.05) and myocardial infarction (MI)/non-fatal MI (HR 0.84; 95% CI 0.70-1.00; p = 0.046).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143311
13HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with reduced ejection fraction, pooled GLP-1 receptor agonists reduced cardiovascular death (HR 0.71).
In plain wordsIn people with reduced-ejection-fraction heart failure, pooled GLP-1 drugs lowered heart-related death.
Peptide
Semaglutide
Outcome
DecreaseCardiovascular death in HFrEF
Study
n: not reported in source
Outcome group
Mortality · Cardiovascular
Measurements
HR
0.71 ratio
HFrEF, cardiovascular death
Source sentences
Summary
In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143309
14HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In heart failure subgroups of cardiovascular outcome trials, pooled GLP-1 receptor agonists reduced myocardial infarction (HR 0.84).
In plain wordsIn people with heart failure from large cardiovascular trials, pooled GLP-1 drugs lowered heart attacks.
Peptide
Semaglutide
Outcome
DecreaseMyocardial infarction in HF subgroups from CVOTs
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.84 ratio
CVOT HF subgroups, MI
Source sentences
Summary
Trial-level analyses showed that cardiovascular benefits were primarily observed in HF subgroups from CVOTs, including reductions in MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001), cardiovascular death (HR 0.88; 95% CI 0.77-1.00; p = 0.05) and myocardial infarction (MI)/non-fatal MI (HR 0.84; 95% CI 0.70-1.00; p = 0.046).
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143312
15HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, pooled GLP-1 receptor agonists improved functional capacity.
In plain wordsIn people with preserved-ejection-fraction heart failure, pooled GLP-1 drugs improved physical capacity.
Peptide
Semaglutide
Outcome
IncreaseFunctional capacity in HFpEF
Study
n: not reported in source
Outcome group
Exercise and physical function · Cardiovascular
Source sentences
Summary
GLP-1 RAs also improved functional capacity and quality of life in HFpEF.
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143313
16HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients with heart failure with preserved ejection fraction, pooled GLP-1 receptor agonists improved quality of life.
In plain wordsIn people with preserved-ejection-fraction heart failure, pooled GLP-1 drugs improved quality of life.
Peptide
Semaglutide
Outcome
IncreaseQuality of life in HFpEF
Study
n: not reported in source
Outcome group
Quality of life · Cardiovascular
Source sentences
Summary
GLP-1 RAs also improved functional capacity and quality of life in HFpEF.
1 context sentence(design, population, supporting numbers)
Summary · context
This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4279143314

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

PepBank is a research reference. Talk to a doctor before you use any peptide.