Glucagon-like peptide-1 receptor agonists for prevention of heart failure events in type 2 diabetes and/or obesity.

Raveendra K, Joseph T, Kang J, Hurdus B, Cutting U, Haris M, Younsi T, Aslam A, Petrie M, Metra M, Ajjan RA, Wu J, Gale CP, Nadarajah R

ESC heart failure1 Mar 2026

PMID41883191PMCIDPMC13064920DOI10.1093/eschf/xvag091PepBankPUB-41883191

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Summary

IntroductionHeart failure (HF) is a common sequela of diabetes and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists may prevent HF events. This meta-analysis estimates absolute risk reduction (ARR) and number needed to treat (NNT) for GLP-1 receptor agonists to prevent one HF event in patients with type 2 diabetes and/or obesity, including those without baseline HF.MethodsThe Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint. Random effects meta-analysis using the Mantel-Haenszel Method was performed to synthesize risk ratios (RR), ARRs, and NNTs with 95% confidence intervals (CI).ResultsTwelve placebo-controlled RCTs involving 95 023 patients were included. GLP-1 receptor agonists reduced HF events by 12% (RR 0.88, 95% CI 0.82-0.95; ARR 0.42%, 95% CI 0.17%-0.62%; NNT 238, 95% CI 161-588), and, in those without baseline HF, by 19% (RR 0.81, 95% CI 0.72-0.90; ARR 0.60%, 95% CI 0.32%-0.89%; NNT 167, 95% CI 113-313). Semaglutide reduced the risk of HF events by 16% (RR 0.84, 95% CI 0.74-0.95; ARR 0.62%, 95% CI 0.19%-1.00%; NNT 161, 95% CI 100-526), and by 31% in those without baseline HF (RR 0.69, 95% CI 0.55-0.88; ARR 1.25%, 95% CI 0.48%-1.82%; NNT 80, 95% CI 55-208).ConclusionGLP-1 receptor agonists have limited absolute benefit for preventing HF events in patients with type 2 diabetes and/or obesity, including in those without baseline HF.Systematic review registrationPROSPERO: CRD420251074882.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

01HumanSystematic reviewEfficacy outcome
In patients with type 2 diabetes and/or obesity, semaglutide reduced the risk of heart failure events by 16% versus placebo.
In plain wordsIn people with type 2 diabetes and/or obesity, semaglutide reduced heart failure events by 16% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseHeart failure events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
RR
0.84 ratio
semaglutide
ARR
0.62%
semaglutide
NNT
161 patients
semaglutide
Source sentences
Summary
Semaglutide reduced the risk of HF events by 16% (RR 0.84, 95% CI 0.74-0.95; ARR 0.62%, 95% CI 0.19%-1.00%; NNT 161, 95% CI 100-526)
1 context sentence(design, population, supporting numbers)
Summary · context
The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint.
Show in the study text Report a problemFND-4188319103
02HumanSystematic reviewEfficacy outcome
In patients without baseline heart failure, semaglutide reduced the risk of heart failure events by 31% versus placebo.
In plain wordsIn people without heart failure at the start, semaglutide reduced heart failure events by 31% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseHeart failure events in patients without baseline heart failure
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
RR
0.69 ratio
semaglutide, no baseline HF
ARR
1.25%
semaglutide, no baseline HF
NNT
80 patients
semaglutide, no baseline HF
Source sentences
Summary
and by 31% in those without baseline HF (RR 0.69, 95% CI 0.55-0.88; ARR 1.25%, 95% CI 0.48%-1.82%; NNT 80, 95% CI 55-208)
2 context sentences(design, population, supporting numbers)
Summary · context
Semaglutide reduced the risk of HF events
Summary · context
The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint.
Show in the study text Report a problemFND-4188319104

Studies that did not test the peptide alone2

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 type 2 diabetes and/or obesity, pooled GLP-1 receptor agonists reduced heart failure events by 12% versus placebo.
In plain wordsIn people with type 2 diabetes and/or obesity, GLP-1 drugs as a group reduced heart failure events by 12% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseHeart failure events
Study
n = 95,023
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
RR
0.88 ratio
all GLP-1 receptor agonists
ARR
0.42%
all GLP-1 receptor agonists
NNT
238 patients
all GLP-1 receptor agonists
Source sentences
Summary
GLP-1 receptor agonists reduced HF events by 12% (RR 0.88, 95% CI 0.82-0.95; ARR 0.42%, 95% CI 0.17%-0.62%; NNT 238, 95% CI 161-588)
1 context sentence(design, population, supporting numbers)
Summary · context
The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint.
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.
Show in the study text Report a problemFND-4188319101
04HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In patients without baseline heart failure, pooled GLP-1 receptor agonists reduced heart failure events by 19% versus placebo.
In plain wordsIn people without heart failure at the start, GLP-1 drugs as a group reduced heart failure events by 19% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseHeart failure events in patients without baseline heart failure
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
RR
0.81 ratio
all GLP-1 receptor agonists, no baseline HF
ARR
0.6%
all GLP-1 receptor agonists, no baseline HF
NNT
167 patients
all GLP-1 receptor agonists, no baseline HF
Source sentences
Summary
and, in those without baseline HF, by 19% (RR 0.81, 95% CI 0.72-0.90; ARR 0.60%, 95% CI 0.32%-0.89%; NNT 167, 95% CI 113-313)
1 context sentence(design, population, supporting numbers)
Summary · context
The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint.
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.
Show in the study text Report a problemFND-4188319102

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

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