Investigation of the haemodynamic effects of exenatide in healthy male subjects

Mendis, Buddhike; Simpson, Elizabeth; Macdonald, Ian; Mansell, Peter

Abstract

AIMS In clinical studies of glucagon-like peptide-1 (GLP-1) agonists used in the management of patients with type 2 diabetes, there is often a small accompanying fall in blood pressure. The mechanism underlying this effect is not known, although exenatide, a GLP-1 mimetic, has acute regional vasodilator properties in rats. We have therefore studied the haemodynamic effects of exenatide in healthy male volunteers. METHODS We compared the effects of a single 10μg subcutaneous injection of exenatide with placebo in a double-blind, randomized, crossover study. For 2h after dosing, haemodynamic measurements were made using a Finometer, venous occlusion plethysmography and Doppler ultrasound. The urine sodium:creatinine excretion ratio was determined. RESULTS At the end of the study when exenatide was compared with placebo, heart rate had risen by a mean of 8.2 (95% CI 4.2, 12.2, P < 0.01) beatsmin-1, cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) lmin-1 and total peripheral resistance had fallen by 120 (95% CI -8, -233, P < 0.05) dynscm-5.There were no differences in blood pressure. The urinary sodium:creatinine ratio was increased by mean 12.4 (95% CI 4.6, 20.2, P < 0.05) mmolmmol-1 when exenatide was compared with placebo. CONCLUSIONS Exenatide has significant haemodynamic effects in healthy volunteers. The results of this study are consistent with exenatide having both vasodilator and natriuretic properties. The vascular changes may contribute to the hypotensive effect of exenatide when used chronically in patients with diabetes. © 2012 The British Pharmacological Society.

Citation

Mendis, B., Simpson, E., Macdonald, I., & Mansell, P. (2012). Investigation of the haemodynamic effects of exenatide in healthy male subjects. British Journal of Clinical Pharmacology, 74(3), 437-444. https://doi.org/10.1111/j.1365-2125.2012.04214.x

• Journal Article Type: Article
• Acceptance Date: Jan 24, 2012
• Online Publication Date: Feb 9, 2012
• Publication Date: Sep 1, 2012
• Deposit Date: Jan 20, 2023
• Journal: British Journal of Clinical Pharmacology
• Print ISSN: 0306-5251
• Electronic ISSN: 1365-2125
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Issue: 3
• Pages: 437-444
• DOI: https://doi.org/10.1111/j.1365-2125.2012.04214.x
• Public URL: https://nottingham-repository.worktribe.com/output/3101384
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2012.04214.x