Effects of GLP-1 Agonists on mortality and arrhythmias in patients with Type II diabetes

Background: Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RA) are frequently used for the management of diabetes. The impact of GLP-1 RA on cardiovascular outcomes is unclear. We aim to assess the effect of GLP-1 RA on mortality, atrial and ventricular arrhythmias, and sudden cardiac death in patients with type II diabetes. Methods: We searched databases including Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar and CINAHL, from inception to May 2022, for randomized controlled trials reporting the relationship between GLP-1 RA (including albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide) and mortality, atrial arrhythmias, and the combined incidence of ventricular arrhythmias and sudden cardiac death. The search was not restricted to time or publication status. Results: A total of 464 studies resulted from literature search, of which 44 studies, including 78,702 patients (41,800 GLP-1 agonists vs 36,902 control), were included. Follow up ranged from 52 to 208 weeks. GLP-1 RA were associated with lower risk of all-cause mortality (odds ratio 0.891, 95% confidence interval 0.837–0.949; P < 0.01) and reduced cardiovascular mortality (odds ratio 0.88, 95% confidence interval 0.881–0.954; P < 0.01). GLP-1 RA were not associated with increased risk of atrial (odds ratio 0.963, 95% confidence interval 0.869–1.066; P 0.46) or ventricular arrhythmias and sudden cardiac death (odds ratio 0.895, 95% confidence interval 0.706–1.135; P 0.36). Conclusion: GLP-1 RA are associated with decreased all-cause and cardiovascular mortality, and no increased risk of atrial and ventricular arrhythmias and sudden cardiac death.