Meta-analysis of cardiovascular outcome trials assessing the impact of glucagon-like peptide-1 receptor agonists on major cardiac arrhythmias

Objective Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a group of novel antidiabetic agents, demonstrated beneficial cardiovascular effects in recent large, placebo-controlled randomised clinical trials (RCTs); their clear antiarrhythmic benefit has not been yet underlined. The purpose of the present meta-analysis is to clarify the impact of GLP-1RAs on different types of cardiac arrhythmias. Methods We searched PubMed from its inception up to 8 October 2020 for all available cardiovascular and renal outcome, placebo-controlled RCTs utilising GLP-1RAs versus placebo. The present meta-analysis is reported according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement. Results We included data from 7 RCTs with GLP-1RAs in a total of 55,943 participants. Treatment with GLP-1RAs did not provide significant benefit in the risk for atrial fibrillation (RR = 0.81, 95%CI; 0.78-1.15, I-2 = 51%), atrial flutter (RR = 0.79, 95%CI; 0.53-1.16, I-2 = 0%), ventricular fibrillation (RR = 0.99, 95%CI; 0.48-2.04, I-2 = 0%), ventricular tachycardia (RR = 1.41, 95%CI; 0.87-2.28, I-2 = 10%), atrial tachycardia (RR = 0.63, 95%CI; 0.10-3.90, I-2 = 24%), sinus node dysfunction (RR = 0.70, 95%CI; 0.40-1.23, I-2 = 0%), ventricular extrasystoles (RR = 1.37, 95%CI; 0.56-3.30, I-2 = 0%), second-degree atrioventricular block (RR = 0.96, 95%CI; 0.52-1.74, I-2 = 0%) or complete atrioventricular block (RR = 0.78, 95%CI; 0.39-1.54, I-2 = 38%). Conclusions In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias.