Differential effects of glucagon-like peptide-1 receptor agonists on heart rate

Jan 15, 2017Cardiovascular diabetology

Different glucagon-like peptide-1 drugs have varying effects on heart rate

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Short-acting GLP-1 receptor agonists are associated with a transient mean heart rate increase of 1-3 beats per minute.

Long-acting GLP-1 receptor agonists show more pronounced mean heart rate increases, with liraglutide and albiglutide associated with increases of 6-10 beats per minute.
Dulaglutide and exenatide LAR are linked to lower heart rate increases of 3-4 beats per minute.
Heart rate increases from liraglutide and dulaglutide occur both during the day and at night.
In head-to-head trials, lixisenatide resulted in a small, transient heart rate increase, while liraglutide caused a significantly greater and sustained increase over 24 hours.
The mechanism behind the heart rate increase may involve effects on the sinus node or sympathetic nervous system stimulation, potentially linked to the duration of action of GLP-1 receptor agonists.
A GLP-1 receptor agonist-induced heart rate increase does not appear to raise cardiovascular risk in subjects with type 2 diabetes, although pronounced increases may be linked to adverse outcomes in advanced heart failure.

AI simplified

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms). HR effects observed in two independent head-to-head trials of lixisenatide and liraglutide (N = 202; active-treatment arms) are also reviewed. Short-acting GLP-1 RAs, exenatide and lixisenatide, are associated with a transient (1-12 h) mean placebo- and baseline-adjusted 24-h HR increase of 1-3 beats per minute (bpm). Conversely, long-acting GLP-1 RAs are associated with more pronounced increases in mean 24-h HR; the highest seen with liraglutide and albiglutide at 6-10 bpm compared with dulaglutide and exenatide LAR at 3-4 bpm. For both liraglutide and dulaglutide, HR increases were recorded during both the day and at night. In two head-to-head comparisons, a small, transient mean increase in HR from baseline was observed with lixisenatide; liraglutide induced a substantially greater increase that remained significantly elevated over 24 h. The underlying mechanism for increased HR remains to be elucidated; however, it could be related to a direct effect at the sinus node and/or stimulation of the sympathetic nervous system, with this effect related to the duration of action of the respective GLP-1 RAs. In conclusion, this review indicates that the effects on HR differ within the class of GLP-1 RAs: short-acting GLP-1 RAs are associated with a modest and transient HR increase before returning to baseline levels, while some long-acting GLP-1 RAs are associated with a more pronounced and sustained increase during the day and night. Findings from recently completed trials indicate that a GLP-1 RA-induced increase in HR, regardless of magnitude, does not present an increased cardiovascular risk for subjects with T2DM, although a pronounced increase in HR may be associated with adverse clinical outcomes in those with advanced heart failure.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗

Differential effects of glucagon-like peptide-1 receptor agonists on heart rate

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief