Liraglutide Treatment May Affect Renin and Aldosterone Release.
Nowadays, GLP-1 receptor agonists are widely used as effective and safe antidiabetic medications. In addition to glucose-dependent insulin secretion, their effects reach beyond glucose control. Previously, it has been shown that acute administration of GLP-1 receptor agonists increases circulating glucocorticoid and mineralocorticoid levels in both humans and rodents. So far, no studies have reported the effects of chronic administration of GLP-1 receptor agonists on the hypothalamic-pituitary-adrenal axis in humans. The aim of the current study was to examine the effects of acute and chronic treatment with the GLP-1 receptor agonist liraglutide on adrenal function in humans. Ten healthy volunteers were recruited into a single group open-label clinical trial. Each participant was tested for baseline levels, and after acute and chronic treatment with 0.6 mg liraglutide daily. A graded glucose infusion test was performed 3 times. We found that aldosterone tended to be suppressed (albeit not statistically different) after acute administration of liraglutide, and increased after chronic dosing; the difference was statistically significant when compared between acute and chronic dosing. Changes in aldosterone levels followed the changes in renin concentrations and the aldosterone-to-renin ratio remained stable. No statistically significant differences were observed in ACTH or cortisol levels. In conclusion, we have shown that a low dose of GLP-1 receptor agonist may interfere with renin and aldosterone release. Further studies in a larger patient sample and with higher doses of GLP-1 receptor agonists are warranted to corroborate this finding. The study protocol was registered at clinical.trials.gov (NCT02089256) and EU Clinical Trial Register (2014-000238-43).
Department of Physiology, Institute of Biomedicine and Translational Medicine, and Centre of Excellence for Genomics and Translational Medicine University of Tartu, Tartu, Estonia.
Tuuli
T
Sedman
Department of Physiology, Institute of Biomedicine and Translational Medicine, and Centre of Excellence for Genomics and Translational Medicine University of Tartu, Tartu, Estonia.
Keiu
K
Heinla
Department of Physiology, Institute of Biomedicine and Translational Medicine, and Centre of Excellence for Genomics and Translational Medicine University of Tartu, Tartu, Estonia.
Eero
E
Vasar
Department of Physiology, Institute of Biomedicine and Translational Medicine, and Centre of Excellence for Genomics and Translational Medicine University of Tartu, Tartu, Estonia.
Vallo
V
Volke
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000097:blood; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000097:blood; D055815:Young Adult
D007004:Hypoglycemic Agents; D000450:Aldosterone; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D012964:Sodium; D012083:Renin; D011188:Potassium