Investigation of the haemodynamic effects of exenatide in healthy male subjects.
Author(s): Mendis B, Simpson E, MacDonald I, Mansell P.
Affiliation(s): School of Biomedical Sciences, Medical School, University of Nottingham, UK.
buddhike@doctors.org.uk
Publication date & source: 2012, Br J Clin Pharmacol. , 74(3):437-44
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 10 µg subcutaneous injection of
exenatide with placebo in a double-blind, randomized, crossover study. For 2 h
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) beats min(-1) ,
cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) l min(-1) and total
peripheral resistance had fallen by 120 (95% CI -8, -233, P < 0.05) dyn s cm(-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) mmol mmol(-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.
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