GLP-1 RAs not associated with arrhythmia risk and impart positive cardiovascular safety

A new study by Sijin Wu and team shows that the use of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not increase arrhythmia risk, indicating a positive cardiovascular safety profile. The findings of this study were published in The Diabetology & Metabolic Syndrome.

For glycemic management and weight loss, glucagon-like peptide-1 receptor agonists have received strong recommendations. But there is growing proof that using GLP-1 RAs causes a rise in heart rate, which has the potential to cause cardiac arrhythmias. In order to better understand how GLP-1 RA treatment affects incidence arrhythmias in diabetes and obese individuals, this study was done.

From the beginning through May 25, 2022, EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov were all thoroughly searched. For adults with type 2 diabetes or obesity, randomized controlled trials (RCTs) contrasting GLP-1 RAs with placebo or active control were included. Atrial fibrillation (AF), ventricular arrhythmias (VAs), atrial flutter (AFL), and sudden cardiac death were specified as the outcomes of interest (SCD). 

The key findings of this study were:

1.56 RCTs totaling 79,720 people (mean age 57.3 years; 44,028 GLP-1 RAs versus 35,692 controls) were included from 7692 citations.

2.In comparison to controls, the use of GLP-1 RAs did not substantially enhance the risk of AF, AFL, VAs, or SCD.

3.In additional subgroup analyses, a rising tendency toward incident AF was shown with dulaglutide whereas a reversing trend was seen with oral semaglutide.

4.Furthermore, greater baseline BMI and GLP-1 RA dosages may dramatically raise the incidence of VAs.

5.Other subgroup analyses did not reveal any changes that were statistically significant.

In diabetic and obese individuals, GLP-1 RA treatment was generally not substantially linked with incidence arrhythmias, suggesting a reassuring cardiovascular safety profile. While dulaglutide showed the opposite effect, oral semaglutide may be linked to a decreased incidence of incident AF. Notably, doctors should exercise greater caution when treating obese patients or administering excessive dosages due to the higher risk of VAs. Further research is necessary to determine if the putative antiarrhythmic or arrhythmogenic action of GLP-1 RAs is drug-specific.

Reference:

Wu, S., Lu, W., Chen, Z., Dai, Y., Chen, K., & Zhang, S. (2022). Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: a systematic review and meta-analysis of randomized controlled trials. In Diabetology & Metabolic Syndrome (Vol. 14, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s13098-022-00970-2