Effects of glucagon-like peptide-1 receptor agonists on copeptin in healthy volunteers and patients with primary polydipsia

Svenja Leibnitz; Mirjam Christ-Crain; Bettina Winzeler

doi:10.1530/endoabs.93.OC10

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Endocrine Abstracts (2023) 93 OC10 | DOI: 10.1530/endoabs.93.OC10

EYES2023 ESE Young Endocrinologists and Scientists (EYES) 2023 Oral communication 2: Neuroendocrinology (6 abstracts)

Effects of glucagon-like peptide-1 receptor agonists on copeptin in healthy volunteers and patients with primary polydipsia

Svenja Leibnitz , Mirjam Christ-Crain & Bettina Winzeler

Err

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University Hospital of Basel, Department of Endocrinology, Basel, Switzerland.

Background: Today, GLP-1 receptor agonists have great clinical importance in the treatment of type 2 diabetes and obesity. Furthermore, GLP-1 seems to play a significant role in sodium and water homeostasis. Recent findings investigating long-term effects of treatment with GLP-1 receptor agonists showed a reduction of fluid intake irrespective of food consumption. To our knowledge, data regarding physiological mechanisms that could explain these observations are inconclusive. Furthermore, no effect of GLP-1 on Vasopressin has been observed to date.

Objectives: The aim of this secondary analysis was to investigate changes of Copeptin levels in euvolemic participants treated with dulaglutide versus placebo. We hypothesize that dulaglutide effects a stimulation in Vasopressin due to reduced water intake, lowered blood pressure and nausea which are known side effects of GLP-1 receptor agonists.

Methods: A secondary analysis of randomized, double-blind, placebo-controlled, crossover-trials in 20 healthy participants (GATE trial) and 34 patients with primary polydipsia (GOLD trial) was performed at the University Hospital of Basel. In both studies participants received either Dulaglutide (Trulicity®) 1.5 mg or placebo, in random order, subcutaneously once weekly over a three-week treatment phase. After a wash-out period of at least three weeks, patients received the complementary intervention. The primary objective was to investigate the effect of a three-week treatment with Dulaglutide on Copeptin levels in euvolemic adults.

Results: All 54 participants of the two cross-over trials were included. Median age was 27 (IQR 24 to 37) years and 63% were female. After a three-week treatment phase, Dulaglutide showed a significant suppression of Copeptin in both trials (P=0.04) compared to placebo [GOLD: treatment effect: −0.67pmol/l versus GATE: treatment effect: −1 pmol/l].

Conclusion: This analysis will provide further information on the direct effects of GLP-1 on Vasopressin and could reveal physiological mechanisms that explain the role of GLP-1 in sodium and water balance.