Comparative Effectiveness of Glucagon-like Peptide-1- Receptor Agonists in Patients With Heart Failure With Preserved or Minimally Reduced Ejection Fraction: A Comprehensive Bayesian Network Meta-Analysis and Network Meta-Regression.

Khalil I, Islam MR, Kamrul-Hasan ABM, Nagendra L, Promi SA, Sayed MA, Rahman MT, Sultana N, Tasmi NA, Das M, Tarannum S, Dey R, Dutta D

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists18 Jun 2025Cited by 10 (Europe PMC)

PMID40553959DOI10.1016/j.eprac.2025.06.005PepBankPUB-40553959

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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 study14

12 results from studies that gave the peptide. 12 results from people.

01HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, semaglutide reduced the risk of hospitalization for heart failure versus placebo.
In plain wordsIn pooled trials of people with heart failure, semaglutide lowered the risk of hospital stays for heart failure compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseHospitalization for heart failure
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
HR for HF hospitalization
0.52 HR
semaglutide vs placebo
Source sentences
Summary
Compared to placebo, semaglutide reduced the risk of HHF (HR 0.52, 95% CrI [0.25, 0.87])
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395901
02HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, tirzepatide showed no significant effect on hospitalization for heart failure versus placebo.
In plain wordsIn pooled trials of people with heart failure, tirzepatide did not clearly change the risk of hospital stays for heart failure compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeHospitalization for heart failure
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
HR for HF hospitalization
0.51 HR
tirzepatide vs placebo
Source sentences
Summary
while tirzepatide (HR 0.51, 95% CrI [0.16, 1.24])
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395902
03HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, semaglutide reduced the risk of all-cause mortality.
In plain wordsIn pooled trials of people with heart failure, semaglutide lowered the risk of death from any cause compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseAll-cause mortality
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide and exenatide, but not tirzepatide, reduced the risk of all-cause mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395903
04HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, tirzepatide did not reduce the risk of all-cause mortality.
In plain wordsIn pooled trials of people with heart failure, tirzepatide did not lower the risk of death from any cause compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeAll-cause mortality
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide and exenatide, but not tirzepatide, reduced the risk of all-cause mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395904
05HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, semaglutide decreased the risk of worsening heart failure events.
In plain wordsIn pooled trials of people with heart failure, semaglutide lowered the risk of worsening heart failure compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseWorsening of heart failure events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide decreased the risk of worsening of HF events; tirzepatide did not.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395907
06HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, tirzepatide did not decrease the risk of worsening heart failure events.
In plain wordsIn pooled trials of people with heart failure, tirzepatide did not lower the risk of worsening heart failure compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeWorsening of heart failure events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide decreased the risk of worsening of HF events; tirzepatide did not.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395908
07HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, semaglutide enabled weight loss.
In plain wordsIn pooled trials of people with heart failure, semaglutide led to weight loss compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseBody weight
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Tirzepatide and semaglutide enabled weight loss; however, only semaglutide notably enhanced the 6-minute walk distance.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395909
08HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, tirzepatide enabled weight loss.
In plain wordsIn pooled trials of people with heart failure, tirzepatide led to weight loss compared with placebo.
Peptide
Tirzepatide
Outcome
DecreaseBody weight
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Tirzepatide and semaglutide enabled weight loss; however, only semaglutide notably enhanced the 6-minute walk distance.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395910
09HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, semaglutide notably enhanced the 6-minute walk distance.
In plain wordsIn pooled trials of people with heart failure, semaglutide improved how far people could walk in six minutes compared with placebo.
Peptide
Semaglutide
Outcome
Increase6-minute walk distance
Study
n: not reported in source
Comparator
Placebo
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
only semaglutide notably enhanced the 6-minute walk distance.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395911
10HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, tirzepatide did not notably enhance the 6-minute walk distance.
In plain wordsIn pooled trials of people with heart failure, tirzepatide did not clearly improve six-minute walking distance compared with placebo.
Peptide
Tirzepatide
Outcome
No significant change6-minute walk distance
Study
n: not reported in source
Comparator
Placebo
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
only semaglutide notably enhanced the 6-minute walk distance.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
Report a problemFND-4055395912
11HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, tirzepatide ranked highest of the compared GLP-1 receptor agonists for reducing hospitalization for heart failure and body weight.
In plain wordsIn pooled trials of people with heart failure, tirzepatide ranked first among compared GLP-1 drugs for lowering heart failure hospital stays and body weight.
Peptide
Tirzepatide
Outcome
Not applicableTreatment ranking by SUCRA, hospitalization for heart failure and body weight
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
According to the surface under the cumulative ranking curve values, tirzepatide ranked highest for reducing HHF and body weight, semaglutide for decreasing cardiovascular mortality and worsening of HF events and improving the 6-minute walk distance, and exenatide for reducing all-cause mortality.
Report a problemFND-4055395913
12HumanSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, semaglutide ranked highest of the compared GLP-1 receptor agonists for decreasing cardiovascular mortality and worsening of heart failure events and for improving the 6-minute walk distance.
In plain wordsIn pooled trials of people with heart failure, semaglutide ranked first among the compared GLP-1 drugs for heart-related death, worsening heart failure and walking distance.
Peptide
Semaglutide
Outcome
Not applicableTreatment ranking by SUCRA, cardiovascular mortality, worsening heart failure events and 6-minute walk distance
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
According to the surface under the cumulative ranking curve values, tirzepatide ranked highest for reducing HHF and body weight, semaglutide for decreasing cardiovascular mortality and worsening of HF events and improving the 6-minute walk distance, and exenatide for reducing all-cause mortality.
Report a problemFND-4055395914

Studies that did not test the peptide alone2

In this study, the peptide 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 the peptide.

13HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, none of the GLP-1 receptor agonists (including semaglutide) affected cardiovascular mortality.
In plain wordsIn pooled trials of people with heart failure, no GLP-1 drug, semaglutide included, changed the risk of death from heart causes.
Peptide
Semaglutide
Outcome
No significant changeCardiovascular mortality
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Source sentences
Summary
None affected cardiovascular mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
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-4055395905
14HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of RCTs in patients with HFpEF or HFmrEF, none of the GLP-1 receptor agonists (including tirzepatide) affected cardiovascular mortality.
In plain wordsIn pooled trials of people with heart failure, no GLP-1 drug, tirzepatide included, changed the risk of death from heart causes.
Peptide
Tirzepatide
Outcome
No significant changeCardiovascular mortality
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Source sentences
Summary
None affected cardiovascular mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included.
In this study, Tirzepatide 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 Tirzepatide.
Report a problemFND-4055395906

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 3Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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