Effects of GLP-1 Analogues on Fluid Intake in Patients With Primary Polydipsia (The GOLD-Study) (GOLD)

Glucagon like Peptide -1 (GLP-1) receptor agonists are well known to stimulate glucose-induced insulin secretion and to reduce energy intake. Recent findings from animal and human studies suggest a role of GLP-1 in regulating water and salt homeostasis. GLP-1 has been shown to reduce fluid intake after an oral salt load or during a meal - pointing to a hypodipsic effect. The aim of this study is to elucidate whether these putative hypodipsic properties of GLP-1 might be of advantage in persons with an exaggerated thirst perception as is the case in patients with primary polydipsia.

GLP-1 analogues are currently used for the treatment of hyperglycaemia associated with type 2 diabetes mellitus and given his properties as a natural satiety hormone, the GLP-1 analogue liraglutide was recently approved by the FDA for weight management. In studies related to the influence of GLP-1 and -analogues in controlling food intake a concomitant reduction of fluid consumption has been observed. The investigators hypothesize that GLP-1 analogues not only modulate appetite and provide satiety but also reduce fluid intake and thirst sensation in humans - especially in those with excessive thirst perception (patients with primary polydipsia). In view of future therapeutic options for these patients we aim to investigate the influence of the long-acting GLP-1 analogue dulaglutide on fluid intake, thirst perception and quality of life in patients with primary polydipsia compared to placebo.

Placebo: 0.5 ml normal saline (0.9% sodium chloride [0.9% sodium chloride (NaCl)]), injection sc via syringe once weekly for 3 weeks.

To assess the influence of dulaglutide on thirst perception and quality of life in patients with primary polydipsia compared to placebo.

Neuronal changes assessed with a functional magnet resonance Imaging between dulaglutide and Placebo Treatment in a subgroup of patients with primary polydipsia

for patients during phase a and b, 3rd week each for 15 patients, 15 matched healthy control subjects

Inclusion Criteria: Age over 18 years Polyuria of > 50 ml/Kg/day Polydipsia of > 3 liters/day Exclusion Criteria: Known or probable central or nephrogenic Diabetes insipidus, expected from patient's history Polyuria secondary to diabetes mellitus, hypokalemia, hypercalcemia Pregnancy Previous treatment with GLP-1 agonists within the last 3 month History of pancreatitis Severe renal insufficiency (eGFR (CKD EPI) <30 ml/min/1,73 m2) Cancer

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Winzeler B, Sailer CO, Coynel D, Zanchi D, Vogt DR, Urwyler SA, Refardt J, Christ-Crain M. A randomized controlled trial of the GLP-1 receptor agonist dulaglutide in primary polydipsia. J Clin Invest. 2021 Oct 15;131(20):e151800. doi: 10.1172/JCI151800.