Effect of glucagon-like peptide-1 receptor agonists on heart rate in non-diabetic individuals with overweight or obesity: a systematic review and pairwise and network meta-analysis of randomized controlled trials.

Zhang Y, Zhang C, Gong X, Cheng P, Fu H, Diao L, Song C

European journal of medical research26 Jan 2026Cited by 1 (Europe PMC)

PMID41582189PMCIDPMC12918571DOI10.1186/s40001-026-03933-9PepBankPUB-41582189

Summary

ObjectivesTo explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.MethodsA comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases was conducted. Mean differences (MDs) were calculated as effect estimates for HR. Pairwise and network meta-analysis were conducted.ResultsTwelve articles were included. Pairwise meta-analysis showed significant association of increase compared with placebo in liraglutide [MD 2.37, 95% confidence interval (CI) 1.86, 2.89], semaglutide (MD = 3.35; 95% CI 1.69, 5.01), orforglipron (MD = 7.30; 95% CI 5.48, 9.12), oral semaglutide (MD = 4.50; 95% CI 3.11, 5.89), tirzepatide (MD = 2.05; 95% CI 0.96, 3.13), retatrutide (MD = 3.46; 95% CI 1.74, 5.18), and total GLP-1RAs (MD = 3.47; 95% CI 2.65, 4.29). Network meta-analysis revealed that orforglipron 36 mg was associated with the most pronounced increase (MD = 9.29; 95% CI 4.45, 13.86), whereas tirzepatide 5 mg was associated with the least increase (MD = 0.52; 95% CI - 2.71, 3.78).ConclusionsGLP-1RAs were associated with the increasing of HR in patients with overweight or obesity. Orforglipron 36 mg was associated with the most pronounced increase, and tirzepatide 5 mg the least.

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

Results from this study10

6 results from studies that gave the peptide. 6 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pairwise meta-analysis found that liraglutide increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, liraglutide raised heart rate more than placebo, in a pooled analysis of trials.
Peptide
Liraglutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Measurements
Mean difference in heart rate
2.37 not stated
liraglutide vs placebo
Source sentences
Summary
Pairwise meta-analysis showed significant association of increase compared with placebo in liraglutide [MD 2.37, 95% confidence interval (CI) 1.86, 2.89]
1 context sentence(design, population, supporting numbers)
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
Show in the study text Report a problemFND-4158218901
02HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pairwise meta-analysis found that semaglutide increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, semaglutide raised heart rate more than placebo, in a pooled analysis of trials.
Peptide
Semaglutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Measurements
Mean difference in heart rate
3.35 not stated
semaglutide vs placebo
Source sentences
Summary
semaglutide (MD = 3.35; 95% CI 1.69, 5.01)
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
Show in the study text Report a problemFND-4158218902
03HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pairwise meta-analysis found that oral semaglutide increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, oral semaglutide raised heart rate more than placebo, in a pooled analysis of trials.
Peptide
Semaglutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
Mean difference in heart rate
4.5 not stated
oral semaglutide vs placebo
Source sentences
Summary
oral semaglutide (MD = 4.50; 95% CI 3.11, 5.89)
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
Show in the study text Report a problemFND-4158218903
04HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pairwise meta-analysis found that tirzepatide increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, tirzepatide raised heart rate more than placebo, in a pooled analysis of trials.
Peptide
Tirzepatide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Measurements
Mean difference in heart rate
2.05 not stated
tirzepatide vs placebo
Source sentences
Summary
tirzepatide (MD = 2.05; 95% CI 0.96, 3.13)
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
Show in the study text Report a problemFND-4158218904
05HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pairwise meta-analysis found that retatrutide increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, retatrutide raised heart rate more than placebo, in a pooled analysis of trials.
Peptide
Retatrutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Measurements
Mean difference in heart rate
3.46 not stated
retatrutide vs placebo
Source sentences
Summary
retatrutide (MD = 3.46; 95% CI 1.74, 5.18)
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
Show in the study text Report a problemFND-4158218905
06HumanSystematic reviewEfficacy outcome
In a network meta-analysis in adults with overweight or obesity without diabetes, tirzepatide 5 mg was associated with the smallest heart rate increase, and the confidence interval included zero.
In plain wordsIn adults with overweight or obesity without diabetes, tirzepatide 5 mg was linked to the smallest heart rate rise among the drugs compared.
Peptide
Tirzepatide
Outcome
No significant changeHeart rate difference versus placebo
Study
n: not reported in source
Outcome group
Heart function · Cardiovascular
Studied dose
5 mgAs given in this study (human).
Measurements
Mean difference in heart rate
0.52 not stated
tirzepatide 5 mg
Source sentences
Summary
whereas tirzepatide 5 mg was associated with the least increase (MD = 0.52; 95% CI - 2.71, 3.78).
1 context sentence(design, population, supporting numbers)
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
Show in the study text Report a problemFND-4158218906

Studies that did not test the peptide alone4

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.

07HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pooled GLP-1 receptor agonists (including liraglutide) increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, GLP-1 drugs as a group raised heart rate more than placebo.
Peptide
Liraglutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Measurements
Mean difference in heart rate
3.47 not stated
total GLP-1RAs vs placebo
Source sentences
Summary
total GLP-1RAs (MD = 3.47; 95% CI 2.65, 4.29).
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
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-4158218907
08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pooled GLP-1 receptor agonists (including semaglutide) increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, GLP-1 drugs as a group raised heart rate more than placebo.
Peptide
Semaglutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Measurements
Mean difference in heart rate
3.47 not stated
total GLP-1RAs vs placebo
Source sentences
Summary
total GLP-1RAs (MD = 3.47; 95% CI 2.65, 4.29).
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
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-4158218908
09HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pooled GLP-1 receptor agonists (including tirzepatide) increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, GLP-1 drugs as a group raised heart rate more than placebo.
Peptide
Tirzepatide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Measurements
Mean difference in heart rate
3.47 not stated
total GLP-1RAs vs placebo
Source sentences
Summary
total GLP-1RAs (MD = 3.47; 95% CI 2.65, 4.29).
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
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.
Show in the study text Report a problemFND-4158218909
10HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, pooled GLP-1 receptor agonists (including retatrutide) increased heart rate compared with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, GLP-1 drugs as a group raised heart rate more than placebo.
Peptide
Retatrutide
Outcome
IncreaseHeart rate difference versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Measurements
Mean difference in heart rate
3.47 not stated
total GLP-1RAs vs placebo
Source sentences
Summary
total GLP-1RAs (MD = 3.47; 95% CI 2.65, 4.29).
2 context sentences(design, population, supporting numbers)
Summary · context
Pairwise meta-analysis showed significant association of increase compared with placebo
Summary · context
To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.
In this study, Retatrutide 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 Retatrutide.
Show in the study text Report a problemFND-4158218910

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 6Current
14 Oct 2026, 01:46 UTC
Study data updated · source update from Europe PMC
Version 5
10 Oct 2026, 10:21 UTC
Study results updated
Versions 2 to 4
9 Oct 2026, 03:07 UTC
The same notice was added 3 times, first on 9 Oct 2026, 03:05 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Effect of glucagon-like peptide-1 receptor agonists on heart rate in non-diabetic individuals with overweight or obesity: a systematic review and pairwise and network meta-analysis of randomized controlled trials.

Summary

Results from this study10

Studies that did not test the peptide alone4

Version history

Subjects

Publication types

Keywords