# 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

## TL;DR

This study finds that GLP-1 receptor agonists increase heart rate in non-diabetic individuals with overweight or obesity, with some drugs causing larger increases than others.

## Contribution

The study is the first to systematically review and meta-analyze the effect of GLP-1RAs on heart rate in non-diabetic overweight or obese individuals.

## Key findings

- GLP-1 receptor agonists significantly increase heart rate compared to placebo.
- Orforglipron 36 mg causes the largest heart rate increase, while tirzepatide 5 mg causes the smallest.
- Network meta-analysis confirms variability in heart rate effects across different GLP-1RA drugs.

## Abstract

To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.

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.

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).

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.

The online version contains supplementary material available at 10.1186/s40001-026-03933-9.