Endocrine Abstracts

The secretion of growth hormone (GH) is under the feedback control of numerous nutritional and endocrine factors. The most widely used endocrine dynamic tests used to diagnose GH deficiency, insulin hypoglycemia test, and glucagon test, are time-consuming and cumbersome both for patients and medical personnel. There is an unmet need for easier to conduct, shorter, and safer diagnostic tests. We and other groups have previously demonstrated that acute administration of glucagon-like peptide-1 receptor agonist (GLP-1RA) moderately stimulated the hypothalamic-pituitary-adrenal axis in healthy volunteers. As GLP-1RAs possess multiple metabolic effects, we hypothesized that they may also affect the secretion of GH.

We report here the results from 2 clinical trials of GLP-1 RAs on GH secretion. In a pilot single-group, open-label clinical trial the effect of a single subcutaneous injection of 10 μg exenatide was tested on healthy volunteers (n=10). Exenatide elicited a robust increase of GH levels compared to pre-treatment values (P<0.05) with the peak occurring around 60-90 minutes in most subjects. Oral semaglutide is the first oral GLP-1 RA available. We next conducted a randomized, placebo-controlled, crossover clinical trial to test the effect of oral semaglutide on GH release. The study included 10 adult healthy volunteers (age 26-47, 5 females, and 5 males). All participants were tested on two occasions that were at least 1 month apart and received randomly oral semaglutide (7 mg) or placebo. Participants were asked to avoid strenuous physical activity the day before testing. Basal fasting (≥ 8 h) blood samples were taken in the morning (8-9 am) after at least 15 minutes of rest. Study medication was taken with up to 40 ml of water. Post-treatment blood samples were drawn 60, 90, 120, 150, 180, and 240 minutes thereafter. The intensity of nausea according to the visual analog scale (0- no nausea, 10 – vomiting) was also registered. The primary endpoint of the study was the change in growth hormone concentration. The effect of oral semaglutide on GH was variable but did induce a clinically significant GH increase in some study subjects. We conclude that GLP-1 RAs hold a promise for a GH stimulation test and further studies are warranted.