Exenatide acutely increases heart rate in parallel with augmented sympathetic nervous system activation in healthy overweight males

• Published in: British journal of clinical pharmacology 2016-04, Vol.81 (4), p.613-620
• Main Authors: Smits, Mark M., Muskiet, Marcel H. A., Tonneijck, Lennart, Hoekstra, Trynke, Kramer, Mark H. H., Diamant, Michaela, Raalte, Daniël H.
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - analysis; Body Mass Index; Clinical Trials; Cross-Over Studies; Exenatide; GLP‐1 receptor agonist; Glucagon-Like Peptide 1 - agonists; haemodynamics; Healthy Volunteers; heart rate; Heart Rate - drug effects; Humans; Lipids - blood; Male; Overweight - blood; Peptides - administration & dosage; Peptides - adverse effects; Peptides - pharmacology; Sympathetic Nervous System - drug effects; sympathetic nervous system activity; Vascular Resistance - drug effects; Venoms - administration & dosage; Venoms - adverse effects; Venoms - pharmacology; Young Adult
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12843

Aim Clinical use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) is consistently associated with heart rate (HR) acceleration in type 2 diabetes patients. We explored the mechanisms underlying this potential safety concern. Methods Ten healthy overweight males (aged 20–27 years) were examined in an open label, crossover study. Automated oscillometric blood pressure measurements and finger photoplethysmography were performed throughout intravenous administration of placebo (saline 0.9%), exenatide (targeting therapeutic concentrations) and a combination of exenatide and the nitric oxide synthase inhibitor L‐NG‐monomethyl arginine (L‐NMMA). Sympathetic nervous system (SNS) activity was measured by heart rate variability and rate‐pressure product. Results Exenatide increased HR by a mean maximum of 6.8 (95% CI 1.7, 11.9) beats min–1 (P