GLP-1 receptor agonists (GLP-1 RAs) are widely used to manage type 2 diabetes and obesity due to their positive effects on cardiovascular health. However, a notable side effect is an increased heart rate, sparking interest in the underlying reasons for this.

In a recent study, Lubberding and Veedfald et al. (2024) explored the cardiovascular effects of GLP-1, particularly its impact on heart rate (1). They used female landrace pigs, chosen for their physiological similarities to humans. An advanced electrical mapping system with a flexible 64-channel multi-electrode array (MEA) was crucial in measuring and analyzing the heart’s electrical activity.

When GLP-1 was administered to the pigs, an increase in heart rate was observed. This increase persisted despite various nerve and drug interventions, suggesting a direct effect of GLP-1 on the heart rather than an indirect systemic influence. Further tests with isolated pig hearts showed that blocking the GLP-1 receptor prevented the heart rate increase, highlighting the receptor’s key role.

The 64-channel MEA helped identify specific sites of electrical changes, especially in the atria and the heart’s conduction system (Figure 5). Detailed analysis showed that GLP-1 affects the pacemaker cells in the sinus node, which regulate heart rhythm. This effect was specific to these cells, indicating a targeted action of GLP-1 on its receptors.

The study provides strong evidence that GLP-1 directly increases heart rate by acting on receptors in the heart’s pacemaker cells. The advanced 64-channel multi-electrode array technology was essential in uncovering these insights, enhancing our understanding of GLP-1’s cardiovascular effects. This research helps doctors and scientists balance the benefits of GLP-1 RAs with their potential side effects.

 

Reference

  1. Lubberding, Anniek Frederike et al. “GLP-1 increases heart rate by a direct action on the sinus node.” Cardiovascular research, cvae120. 4 Jun. 2024, doi:10.1093/cvr/cvae120