Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are antidiabetic drugs with effects beyond antihyperglycemic action. The aim of the study was to examine whether a single dose of exenatide could be used as a stimulation test for the pituitary-adrenal axis. We carried out a single-group, open-label pilot clinical trial in an ambulatory setting. Ten healthy volunteers of both sexes with body weight>65 kg and age between 18–50 years were recruited. After fasting for 12 hours the subjects received 10 μg of exenatide solution subcutaneously. Blood samples were taken before the administration of exenatide and up to 150 minutes thereafter. The primary outcome was the maximal level of cortisol after the administration of exenatide. Single administration of exenatide 10 μg resulted in a modest increase in ACTH and cortisol levels, as compared to untreated values, and a decrease in blood glucose levels. Remarkably, a robust suppression of both renin and aldosterone levels occurred. We showed that acute administration of exenatide in a full therapeutic dose modestly stimulates the hypothalamic-pituitary-adrenal axis but inhibits the renin-aldosterone system. Further research is warranted to confirm this finding in the placebo-controlled study.

中文翻译：

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GLP-1 受体激动剂抑制健康志愿者的醛固酮释放

胰高血糖素样肽 1 受体激动剂 (GLP-1 RA) 是抗糖尿病药物，其作用超出了抗高血糖作用。该研究的目的是检查单剂量艾塞那肽是否可以用作垂体-肾上腺轴的刺激试验。我们在门诊环境中进行了一项单组、开放标签的试点临床试验。招募了10名体重>65 kg、年龄在18-50岁之间的男女健康志愿者。禁食 12 小时后，受试者皮下接受 10 μg 艾塞那肽溶液。在给予艾塞那肽之前和之后的 150 分钟内采集血样。主要结果是艾塞那肽给药后皮质醇的最大水平。单次给予艾塞那肽 10 μg 导致 ACTH 和皮质醇水平适度增加，与未处理的值相比，以及血糖水平的降低。值得注意的是，发生了对肾素和醛固酮水平的强烈抑制。我们表明，以全治疗剂量急性给予艾塞那肽适度刺激下丘脑-垂体-肾上腺轴，但抑制肾素-醛固酮系统。需要进一步研究以证实安慰剂对照研究中的这一发现。