Liraglutide Treatment May Affect Renin and Aldosterone Release

Abstract

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).

Glucagon-Like Peptide-1 Infusion Suppresses Aldosterone Levels in Healthy Normal-Weight Individuals: Double-Blind, Placebo-Controlled Crossover Study

“…In our study, the decrease in aldosterone 3 h after GLP-1 infusion may be explained by the direct action of GLP-1 on its receptors in kidney tissue and the inhibition of angiotensin II. In a study by Sedam et al [ 16 ], the long-term administration of liraglutide increased aldosterone levels. That study showed that aldosterone tended to increase after chronic dosing with liraglutide, yet the aldosterone-to-PRA ratio remained unchanged.…”

Effect of sodium–glucose cotransporter-2 inhibitors on aldosterone-to-renin ratio in diabetic patients with hypertension: a retrospective observational study

“…In fact, pioglitazone, a thiazolidinedione, was reported to suppress the production of aldosterone [45,46]. Liraglutide, a GLP-1 agonist, may also suppress the RASS [47]; nonetheless, the effects of antidiabetic agents on ARR have not been reported. Most patients with PA are also prescribed medications for diabetes, rather than for hypertension alone.…”

The role of glucagon in the possible mechanism of cardiovascular mortality reduction in type 2 diabetes patients

“…Therefore, it is unsuitable to generalise the underlying pathophysiologic mechanisms, based on the early separation and similar effect on mortality seen from survival curves, especially with such huge differences in the baseline characteristics of studied populations. In addition, liraglutide did not show any effect during a short term use, but in chronic use it caused an increase in aldosterone concentrations (Table ) …”