A GLP-1 Receptor Agonist Inhibits Aldosterone Release in Healthy Volunteers

Abstract

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.

Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System

“…Although data from literature indicate that GLP-1 inhibits ANG II action, its effect on aldosterone is less established. Baretic et al (92) and more recently Heinla et al (68) reported that a single GLP-1 infusion decreased aldosterone levels in healthy, normal weight subjects. Conversely, both Skov et al (65) and Asmar et al (66) did not find changes in aldosterone concentrations under comparable conditions.…”

“…( 92 ) and more recently Heinla et al. ( 68 ) reported that a single GLP-1 infusion decreased aldosterone levels in healthy, normal weight subjects. Conversely, both Skov et al.…”

“…Both acute GLP-1 infusion (65, 66) and a single liraglutide dose (67) decreased plasma ANG II concentration in healthy subjects and type 2 diabetic patients, consistently with an inhibitory effect of GLP-1 on renin secretion (68,69). However, the underlying mechanism has not been fully elucidated.…”

in vivo mapping of hemodynamic responses mediated by tubuloglomerular feedback in healthy and hypertensive rat kidneys

“…However, other pathways that GLP-1RAs could affect renal hemodynamics should be considered in interpreting our results. For example, clinical evidence suggests that GLP-1RA might counteract angiotensin II activity (RAAS) 54,55 , which is a sign of renoprotection against diabetic nephropathy 56 . Plus, certain neural and metabolic pathways are also thought to be involved in GLP-1RA-induced renal hemodynamic changes 57 .…”

Emerging Perspectives on the Impact of Diabetes Mellitus and Anti-Diabetic Drugs on Premenstrual Syndrome. A Narrative Review

“…As regards the endocrinal effects, despite the shortage of information on the clinical effects of GLP-1/GLP-1RAs on the hypothalamic–pituitary–ovarian hormones, experimental studies have demonstrated a potent effect of GLP-1RAs on regulating the hypothalamic–pituitary–adrenal axis. GLP-1RAs can suppress aldosterone production, which may improve fluid retention in the premenstrual phase [ 141 ]. In rats, GLP-1RAs also exhibited a positive impact on estradiol and progesterone levels along the estrous cycle [ 142 ].…”