['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.', 'Ten healthy overweight males (aged 20-27\xa0years) 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-N(G) -monomethyl arginine (L-NMMA). Sympathetic nervous system (SNS) activity was measured by heart rate variability and rate-pressure product.', 'Exenatide increased HR by a mean maximum of 6.8 (95% CI 1.7, 11.9) beats\xa0min(-1) (P\xa0<\xa00.05), systolic blood pressure (SBP) by 9.8 (95% CI 3.5, 16.1) mmHg (P\xa0<\xa00.01) and markers of SNS activity (P\xa0<\xa00.05). No changes in total peripheral resistance were observed. Increases in HR, SBP and sympathetic activity were preserved during concomitant L-NMMA infusion.'] Does exenatide acutely increase heart rate in parallel with augmented sympathetic nervous system activation in healthy overweight males?