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

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.