Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of double-blind, randomized, placebo-controlled clinical trials.

Qin J, Song L

BMC endocrine disorders12 May 2022Cited by 26 (Europe PMC)

PMID35546664PMCIDPMC9097124DOI10.1186/s12902-022-01036-0PepBankPUB-35546664

Summary

BackgroundThe cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients.MethodsPubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke.ResultsWe included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 - 1.01; P = 0.06).ConclusionWe concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes.

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

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

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.

01HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists (including liraglutide) reduced the risk of death from cardiovascular causes versus placebo.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs, liraglutide among them, lowered the risk of cardiovascular death compared with placebo.
Peptide
Liraglutide
Outcome
DecreaseDeath from cardiovascular causes
Study
n = 52,821
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Relative risk
0.9
cardiovascular death, pooled GLP-1 receptor agonists
Source sentences
Summary
The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls.
1 context sentence(design, population, supporting numbers)
Summary · context
We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-3554666401
02HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists (including liraglutide) reduced the risk of fatal or non-fatal stroke versus placebo.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs, liraglutide among them, lowered the risk of stroke compared with placebo.
Peptide
Liraglutide
Outcome
DecreaseFatal or non-fatal stroke
Study
n = 52,821
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Relative risk
0.85
stroke, pooled GLP-1 receptor agonists
Source sentences
Summary
The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls.
1 context sentence(design, population, supporting numbers)
Summary · context
We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-3554666402
03HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists (including liraglutide) did not significantly change fatal or non-fatal myocardial infarction versus placebo.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs, liraglutide among them, did not significantly change heart attack risk compared with placebo.
Peptide
Liraglutide
Outcome
No significant changeFatal or non-fatal myocardial infarction
Study
n = 52,821
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Relative risk
0.91
myocardial infarction, pooled GLP-1 receptor agonists
Source sentences
Summary
But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 - 1.01; P = 0.06).
1 context sentence(design, population, supporting numbers)
Summary · context
We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-3554666403
04HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists (including semaglutide) reduced the risk of death from cardiovascular causes versus placebo.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs, semaglutide among them, lowered the risk of cardiovascular death compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseDeath from cardiovascular causes
Study
n = 52,821
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Relative risk
0.9
cardiovascular death, pooled GLP-1 receptor agonists
Source sentences
Summary
The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls.
1 context sentence(design, population, supporting numbers)
Summary · context
We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients.
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-3554666404
05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists (including semaglutide) reduced the risk of fatal or non-fatal stroke versus placebo.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs, semaglutide among them, lowered the risk of stroke compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseFatal or non-fatal stroke
Study
n = 52,821
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Relative risk
0.85
stroke, pooled GLP-1 receptor agonists
Source sentences
Summary
The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls.
1 context sentence(design, population, supporting numbers)
Summary · context
We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients.
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-3554666405
06HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists (including semaglutide) did not significantly change fatal or non-fatal myocardial infarction versus placebo.
In plain wordsIn adults with type 2 diabetes, pooled GLP-1 drugs, semaglutide among them, did not significantly change heart attack risk compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeFatal or non-fatal myocardial infarction
Study
n = 52,821
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Relative risk
0.91
myocardial infarction, pooled GLP-1 receptor agonists
Source sentences
Summary
But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 - 1.01; P = 0.06).
1 context sentence(design, population, supporting numbers)
Summary · context
We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients.
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-3554666406

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.

Versions 4 to 5Current
27 Oct 2026, 16:36 UTC
The same notice was added 2 times, first on 21 Oct 2026, 18:59 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 3
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:06 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of double-blind, randomized, placebo-controlled clinical trials.

Summary

Results from this study6

Studies that did not test the peptide alone6

Version history

Subjects

Publication types

MeSH terms

Keywords