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.