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
- Design
- Meta-analysis · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationPeople without diabetes, so closer to the reference population than most trial evidence, but overweight or obesity was still required in every included trial.
- Could weight loss explain it?
- Unclear[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2Systematic review with pairwise and network meta-analysis of RCTs; heart rate is a physiological surrogate; the abstract does not report certainty grading or risk-of-bias results. Abstract-level appraisal.
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
Across 12 trials in people with overweight or obesity and no diabetes, each GLP-1-based drug, pooled across doses, raised resting heart rate by a few beats per minute; retatrutide about 3.5 and the oral drug orforglipron the most, about 7. In the network analysis the smallest increase (tirzepatide 5 mg) was not statistically significant. A small effect whose long-term meaning is unknown.
01Findings
What the study reported
- Drugs
- Semaglutide, Liraglutide, Orforglipron, Tirzepatide, Retatrutide
- Comparator
- placebo
- Primary outcome
- Change in resting heart rate vs placebo in adults with overweight or obesity without diabetes (pairwise and network meta-analysis, 12 RCT reports)
- Effect
- All GLP-1 RA-based agents pooled +3.47 bpm; retatrutide +3.46; orforglipron +7.30; semaglutide +3.35; liraglutide +2.37; tirzepatide +2.05. Network: orforglipron 36 mg largest (+9.29), tirzepatide 5 mg smallest (+0.52)
- 95% confidence interval
- Pooled 2.65 to 4.29; retatrutide 1.74 to 5.18; orforglipron 36 mg 4.45 to 13.86
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Obesity status
- overweight or obesity required
- Diabetes status
- no diabetes
Study quality details
- Study design
- Meta-analysis
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- not stated
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: Pooled 2.65 to 4.29; retatrutide 1.74 to 5.18; orforglipron 36 mg 4.45 to 13.86
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- Not reported in the abstract; full text not checked.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[OBJECTIVES] To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes. [METHODS] A 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. [RESULTS] Twelve 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). [CONCLUSIONS] GLP-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.