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Effects of glucagon-like peptide-1 receptor agonists on fluid intake in healthy volunteers

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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.

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Acknowledgements

We thank our volunteers for the participation in our study. In addition, we thank the support staff, study and laboratory personnel at the University Hospital Basel, especially Nina Hutter, Cemile Bathelt, Céline Bürgi, Karin Wild und Silke Purschke for their most helpful support during the study.

Funding

The study was investigator initiated and was supported by a grant from the Swiss National Foundation to M. Christ-Crain (SNF-162608) and the University Hospital Basel, Switzerland.

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Authors and Affiliations

  1. Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland

    Bettina Winzeler, Ismael da Conceição, Julie Refardt, Clara O. Sailer & Mirjam Christ-Crain

  2. Department of Clinical Research, University Hospital Basel, Basel, Switzerland

    Bettina Winzeler, Ismael da Conceição, Julie Refardt, Clara O. Sailer, Gilles Dutilh & Mirjam Christ-Crain

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  1. Bettina Winzeler
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Correspondence to Bettina Winzeler.

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Ethical approval

The study protocol and study medication were approved by both the local ethic committee and the national agency for the authorization and supervision of therapeutic products (Swissmedic). All procedures were in accordance with the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from all study participants.

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Winzeler, B., da Conceição, I., Refardt, J. et al. Effects of glucagon-like peptide-1 receptor agonists on fluid intake in healthy volunteers. Endocrine 70, 292–298 (2020). https://doi.org/10.1007/s12020-020-02394-2

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