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.
This systematic review and meta-analysis examined the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and heart rate (HR) changes in people with overweight or obesity who do not have diabetes. Researchers searched four major databases (PubMed, Web of Science, Embase, and Cochrane Library) and ultimately included 12 randomized controlled trials. Using both pairwise and network meta-analysis methods, the study calculated mean differences (MDs) in HR compared to placebo. Pairwise meta-analysis found that all analyzed GLP-1RAs — including liraglutide, semaglutide, orforglipron, oral semaglutide, tirzepatide, retatrutide, and the drug class overall — were associated with statistically significant increases in heart rate versus placebo. Network meta-analysis, which allows indirect comparisons across agents, suggested that orforglipron 36 mg was associated with the most pronounced HR increase, while tirzepatide 5 mg showed the least increase (and its result was not statistically significant). Key limitations include the indirect nature of network comparisons, variability in trial designs and follow-up durations, and the restriction to a non-diabetic population, which limits generalizability. The clinical significance of the observed HR increases was not fully addressed.
Why this grade: This is a systematic review and network meta-analysis of RCTs in humans, providing pooled evidence, but is limited to 12 trials, relies on indirect comparisons for some drug-dose rankings, and does not fully address clinical significance of the HR changes observed.
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.
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