GLP-1 Receptor Agonists Induce Growth Hormone Secretion in Healthy Volunteers.

Abstract

Growth hormone (GH) is an essential regulator of growth, body composition and fuel metabolism and, consequently, GH secretion is under the feedback control of numerous nutritional and endocrine mediators. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to exert pleiotropic effects, including stimulation of the activity of the hypothalamic-pituitary-adrenal axis. As GLP-1RAs exert multiple metabolic effects, we hypothesised that they may also affect the secretion of GH and examined the effect of a short-acting and a long-acting GLP-1 RA on GH secretion. This is a post hoc analysis of data from clinical trials. Two separate single-group open-label clinical trials were carried out in the ambulatory care setting with a duration of 1 and 21days, respectively. Healthy adult male and female volunteers with no chronic illnesses or use of daily medicines were recruited for the study. The two interventions were: study 1, single dose of 10µg exenatide administered subcutaneously (s.c.); study 2, 0.6mg liraglutide administered s.c. once daily for 21days. Administration of a single dose of exenatide (study 1) caused a clear increase in GH levels, peaking between 60 and 120min post-administration. There was also a small but statistically significant decrease in luteinising hormone and testosterone levels 120min after exenatide dosing. Administration of the long-acting GLP-1RA liraglutide daily for 21 days (study 2) elicited an increase in GH levels with no change in insulin-like growth factor-1 (IGF-1) concentrations after 3weeks of treatment. The results show that the administration of GLP-1RAs may elicit an increase in growth hormone levels. GLP-1 signalling may be a novel mechanism of regulation of GH secretion. This finding needs to be replicated in the placebo-controlled trial. NCT02089256 and NCT03160261.