Abstract Body (Do not enter title and authors here): Background and aims
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes mellitus(T2DM) and overweight/obesity, and are increasingly used for the secondary prevention of atherosclerotic cardiovascular disease and heart failure. However, their effect on different types of cardiac arrhythmias is uncertain. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the anti-arrhythmic effect of GLP-1RA therapy.

Methods
We performed a comprehensive systematic search following PRISMA guidelines across five electronic databases (Cochrane, Embase, PubMed, Scopus and Web of Science) to identify all RCTs that evaluated GLP-1RAs in individuals with T2DM or overweight/obesity. We included all placebo-controlled studies that reported data on the following cardiac arrhythmic events: atrial flutter/fibrillation, sick sinus syndrome, supraventricular tachycardia, premature depolarizations, conduction system disease (atrioventricular, bundle branch, and fascicular blocks), and ventricular arrhythmias (tachycardia and fibrillation). Meta-analyses were conducted using a random-effects model and subgroup analyses were performed to estimate odds ratios (OR).

Results
The analysis included 39 RCTs that enrolled 79,674 participants, with an average follow-up time of 78.9 ± 54.5 weeks. Treatment with GLP-1RAs was associated with a 35% reduction in the risk of atrial fibrillation and atrial flutter compared to placebo (OR 0.65, 95% confidence interval [CI] 0.43–0.98; p =0.04) (Figure 1). No significant differences were observed between GLP-1RAs and placebo with respect to other cardiac arrhythmic events (Figure 2). In subgroup analyses, long-acting GLP-1RA use was related with a significantly lower incidence of sick sinus syndrome in individuals with overweight/obesity (OR 0.42, 95% CI 0.19–0.94; p = 0.03), an effect not observed in patients with T2DM (Figure 3).

Conclusions:
Our systematic review of all GLP-1RA RCTs reporting cardiac arrhythmic events found that treatment with GLP-1RA significantly reduces the incidence of atrial fibrillation and atrial flutter but not other arrhythmias. Subgroup analyses suggest a reduction in sick sinus syndrome in patients with overweight/obesity that are being treated with long-acting formulations. Our study provides additional evidence of the benefit of GLP-1RAs. Patients at increased risk of arrhythmias may be prioritized for GLP-1RA therapy.