Effects of glucagon-like peptide-1 receptor agonists on fluid intake in healthy volunteers
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ORIGINAL ARTICLE
Effects of glucagon-like peptide-1 receptor agonists on fluid intake in healthy volunteers Bettina Winzeler 1,2 Ismael da Conceição1,2 Julie Refardt1,2 Clara O. Sailer Mirjam Christ-Crain1,2 ●
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Gilles Dutilh2
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Received: 6 February 2020 / Accepted: 18 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Glucagon-like peptide-1 (GLP-1) receptor agonists (RA) reduce appetite and energy intake. Recent findings from animal studies suggest a role of GLP-1 in drinking and water homeostasis. We aimed to elucidate whether GLP-1 RA reduce fluid intake in healthy volunteers. Methods Double-blind, randomized, placebo-controlled, crossover study. 20 healthy volunteers received dulaglutide 1.5 mg and placebo (0,9% sodium chloride) subcutaneously once weekly for 3 weeks. At the end of each treatment period, participants attended an 8-h evaluation visit, during which they were requested to eat two standardized meals and to drink water ad libitum. The primary outcome was the total fluid intake (ml) during the evaluation visit. Results Mean [SD] age of participants (60% female) was 27 [9.2] years. All but four participants drank less on dulaglutide versus placebo treatment despite identical food intake. The median [IQR] difference of fluid intake on dulaglutide compared to placebo treatment was −100 ml [−400–0]. Median [IQR] total fluid intake was 1300 ml [888–1600] versus 1600 ml [1000–1720], on dulaglutide and placebo treatment, p = 0.06. Median [IQR] 24-h urine output was reduced in dulaglutide versus placebo-treated participants: 1250 ml [975–2080] versus 1680 ml [1400–2040], p = 0.04. Median serum sodium levels were 140 mmol/L on both visits and no difference in thirst perception was noted. Conclusions GLP-1 RA such as dulaglutide seem to modulate fluid balance in humans. This leads us to speculate that GLP-1 RA may be an interesting therapeutic options for patients with excessive drinking behavior e.g., primary polydipsia. Keywords GLP-1 Dulaglutide Hypophysis Pituitary Thirst ●
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Introduction The hormone glucagon-like peptide-1 (GLP-1) is released from enteroendocrine L-cells in the gut as well as centrally by neurons in the nucleus of the solitary tract of the hindbrain in response to food entry in the gastrointestinal tract [1, 2].
Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02394-2) contains supplementary material, which is available to authorized users. * Bettina Winzeler [email protected] 1
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
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Department of Clinical Research, University Hospital Basel, Basel, Switzerland
GLP-1 has a insulinotropic effect [3, 4] and is involved in the regulation of appetite and energy intake [5–7]. These satiating properties make GLP-1 an interesting therapeutic target for body weight control. Indeed, GLP-1 receptor agonists (RA) are widely used as treatment of t
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