Effects of GLP-1 receptor agonists on copeptin in euvolemic participants.

Leibnitz S, Winzeler B, Refardt J, Vogt DR, Sailer CO, Christ-Crain M

European journal of endocrinology1 Feb 2026Cited by 4 (Europe PMC)

PMID41525326DOI10.1093/ejendo/lvag005PepBankPUB-41525326

Publisher page PubMedAsk about this study

Summary

ObjectiveGlucagon-like peptide-1 (GLP-1) plays an important modulatory role in sodium and water homeostasis. Recent studies demonstrated that long-term treatment with GLP-1 receptor agonists (RAs) reduces fluid intake and urine output. To the best of our knowledge, no direct effect of GLP-1 on vasopressin has been observed. This secondary analysis aimed to investigate changes in copeptin levels in euvolemic participants treated with the GLP-1 RA dulaglutide versus placebo.DesignSecondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.MethodsParticipants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly. Blood for copeptin analysis was collected at 08:00 after each treatment phase. To estimate the treatment effect of dulaglutide, we derived the absolute within-subject differences of copeptin between dulaglutide and placebo and used the Wilcoxon rank test for statistical analysis.ResultsAll 54 participants of the two cross-over trials were included. Median age was 27 years [interquartile range (IQR), 24-37.5 years], and 63% were female. Median body mass index (BMI) was 23 kg/m2 (IQR, 20.8-24.8). After 3-week treatment, dulaglutide was associated with a significant suppression of copeptin with a median within-subject difference of -.7 pmol/L (p = .047), corresponding to a 12% reduction compared to placebo. Treatment-induced changes in copeptin were not significantly correlated with GLP-1-mediated reductions in blood pressure, BMI, or incidence of nausea.ConclusionsOur analysis provides evidence that the GLP-1-RA dulaglutide inhibits the vasopressin system and proposes physiological mechanisms that may explain the role of GLP-1 in sodium and water balance.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

1 result from studies that gave the peptide. 1 result from people.

01HumanRandomized controlled trialMechanism
In euvolemic participants, dulaglutide suppressed copeptin by 12% versus placebo.
In plain wordsIn euvolemic participants, dulaglutide lowered copeptin by 12% compared with placebo.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseCopeptin suppression
Study
n = 54
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Studied dose
1.5 mg once weekly · subcutaneous · 3 weeksAs given in this study (human).
Measurements
Copeptin reduction
12%
versus placebo
Median within-subject copeptin difference
−0.7 pmol/L
dulaglutide versus placebo, p = .047
Source sentences
Summary
After 3-week treatment, dulaglutide was associated with a significant suppression of copeptin with a median within-subject difference of -.7 pmol/L (p = .047), corresponding to a 12% reduction compared to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.MethodsParticipants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly.
Show in the study text Report a problemFND-4152532601

Studies that did not test the peptide alone3

In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Dulaglutide (Trulicity).

02HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyMechanism
In euvolemic participants, dulaglutide-induced copeptin changes did not significantly correlate with blood pressure reductions.
In plain wordsIn euvolemic participants, copeptin changes during dulaglutide treatment were not significantly linked to blood pressure reductions.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeCopeptin change correlation with blood pressure
Study
n = 54
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
Treatment-induced changes in copeptin were not significantly correlated with GLP-1-mediated reductions in blood pressure, BMI, or incidence of nausea.
1 context sentence(design, population, supporting numbers)
Summary · context
Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.MethodsParticipants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4152532602
03HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyMechanism
In euvolemic participants, dulaglutide-induced copeptin changes did not significantly correlate with BMI reductions.
In plain wordsIn euvolemic participants, copeptin changes during dulaglutide treatment were not significantly linked to BMI reductions.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeCopeptin change correlation with BMI
Study
n = 54
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
Treatment-induced changes in copeptin were not significantly correlated with GLP-1-mediated reductions in blood pressure, BMI, or incidence of nausea.
1 context sentence(design, population, supporting numbers)
Summary · context
Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.MethodsParticipants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4152532603
04HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyMechanism
In euvolemic participants, dulaglutide-induced copeptin changes did not significantly correlate with nausea incidence.
In plain wordsIn euvolemic participants, copeptin changes during dulaglutide treatment were not significantly linked to nausea.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeCopeptin change correlation with nausea
Study
n = 54
Outcome group
Receptor activity and mechanism · Endocrine and hormones
Source sentences
Summary
Treatment-induced changes in copeptin were not significantly correlated with GLP-1-mediated reductions in blood pressure, BMI, or incidence of nausea.
1 context sentence(design, population, supporting numbers)
Summary · context
Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.MethodsParticipants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4152532604

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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