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

Abstract

Background Type 2 diabetes mellitus poses a significant health burden, whereas growing attention has been focused on the novel classes of antidiabetic drugs. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) constitute such a group of antidiabetic agents. In recent large, placebo-controlled randomized clinical trials (RCTs), GLP-1RAs have demonstrated beneficial cardiovascular effects. Nevertheless, the clear antiarrhythmic benefit has not been underlined yet. Purpose The purpose of the present analysis was to clarify the impact of antidiabetic treatment with GLP-1RAs on the several different types of cardiac arrhythmias, based on data extracted from relevant cardiovascular outcome trials. Methods We searched PubMed plus grey literature for all available cardiovascular and renal outcome, placebo-controlled RCTs utilizing GLP-1RAs versus placebo. Results We pooled data from 7 cardiovascular outcome trials with GLP-1RAs in a total of 55,943 randomized participants patients. When compared to placebo, treatment with GLP-1RAs did not provide a significant benefit in the risk for atrial fibrillation (RR = 0.81, 95% CI: 0.78–1.15, I2=51%) (Figure 1a), atrial flutter (RR=0.79, 95% CI: 0.53–1.16, I2=0%) (Figure 1b), ventricular fibrillation (RR=0.99, 95% CI: 0.48–2.04, I2=0%) (Figure 1c), ventricular tachycardia (RR=1.41, 95% CI: 0.87–2.28, I2=10%) (Figure 1d), atrial tachycardia (RR=0.63, 95% CI: 0.10–3.90, I2=24%) (Figure 2a), sinus node dysfunction (RR=0.70, 95% CI: 0.40–1.23, I2=0%) (Figure 2b), ventricular extrasystoles (RR=1.37, 95% CI: 0.56–3.30, I2=0%) (Figure 2c), second-degree atrioventricular block (RR=0.96, 95% CI: 0.52–1.74, I2=0%) (Figure 2d) or complete atrioventricular block (RR=0.78, 95% CI: 0.39–1.54, I2=38%) (Figure 2e). Conclusions In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Effects of GLP-1 receptor agonists on arrhythmias and its subtypes in patients with type 2 diabetes: A systematic review and meta-analysis

“…The risks of arrhythmias and their subtypes in published high-quality CVOTs of GLP-1RA drug therapy in patients with type 2 diabetes up to March 1, 2022, were therefore extracted, based on this, we also conducted a systematic review and meta-analysis. The novelty of this study is that we included the most recent AMPLITUDE-O trial, which were not included in the 2021 meta-analysis ( 9 ), and we also looked at the risk of hypoglycemia and pneumonia. We included a sample of 60,081 participants from 8 CVOT trials, of which 46,100 had a history of cardiovascular disease (76.7%), and showed that GLP-1RA had no effect on the risk of total arrhythmias [RR=0.96, 95% CI (0.96, 1.05), p =0.36] in patients with type 2 diabetes.…”

“…A 2016 meta-analysis showed that exenatide was associated with an increased risk of arrhythmias in type 2 diabetes (OR 2.83; 95% CI: 1.06-7.57) ( 8 ). In 2021 another linked meta-analysis showed that in type 2 diabetic patients, using GLP-1RA treatment did not significantly affect the risk of major arrhythmia ( 9 ). Thus, it is clear that the controversial findings of before-and-after studies for arrhythmias and the few studies investigating the effect of GLP-1RA on the outcome of different arrhythmia subtypes, together with the recent publication of new RCTs on GLP-1RA on CVD outcome.…”

A meta-analysis evaluating indirectly GLP-1 receptor agonists and arrhythmias in patients with type 2 diabetes and myocardial infarction

“…One meta-analysis included 27 randomized controlled trials (RCTs), of which most used MI as an exclusion criterion, i.e., did not include the T2DM people combined with MI ( 11 ). In another meta-analysis, although all seven RCTs included patients with MI, the proportions varied considerably, e.g., 82.6% of such patients in the ELIXA study but only 16.2% in the REWIND study ( 12 ).…”

“…Besides, some studies reported their neutral relationship. Both Al-Sadawi et al’s ( 11 ) and Boulmpou et al’s ( 12 ) meta-analyses indicated that treatment with GLP-1RAs does not significantly affect the risk for atrial or ventricular arrhythmias.…”