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April 23, 2026Obesity and Endocrinology0 citationsOpen Access

Potential Effect of the Short-Acting GLP-1 Agonist Exenatide on Copeptin in Healthy Adults

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SBSarah BaumannSLSvenja LeibnitzCACihan Atila

Key Result

A single 10 µg exenatide injection in healthy adults produced a non-significant increase in copeptin levels of +0.60 pmol/L at 60 minutes (95% CI -0.46-2.07; p=0.23).

Key Points

  • The study aims to investigate the effect of short-acting GLP-1 receptor agonist exenatide on copeptin levels in healthy adults.
  • Conducted a secondary analysis of a double-blind, placebo-controlled trial.
  • Administered a single 10 µg injection of exenatide and measured copeptin levels at baseline and 60 minutes post-injection.
  • Utilized the Wilcoxon rank test to assess treatment effects on copeptin levels.
  • Copeptin levels showed a mild increase post-injection, with a change of +0.60 pmol/L that was not statistically significant.
  • Excluding those with nausea, the increase in copeptin was +1.06 pmol/L, approaching significance with a p-value of 0.06.
  • A weak negative correlation between GLP-1-induced decreases in blood glucose and copeptin was observed.

Study Design

Type

RCT (n=13)

Blinding

Double-blind

Structured PICO

Does a single 10 µg exenatide injection affect copeptin levels in healthy euvolemic adults?

P
Population
13 healthy euvolemic adults, median age 38 years, 69% male
I
Intervention
Single 10 µg exenatide injection
C
Comparator
Placebo
O
Outcome
Copeptin levels at 60 minutes post-injectionsurrogate

A single 10 µg exenatide injection in healthy adults resulted in a non-significant mild increase in copeptin levels, suggesting a potential modulatory role of GLP-1 on arginine vasopressin regulation.

Main Result

Effect estimate: +0.60 pmol/L (95% CI -0.46-2.07)

p-value: p=0.23

Abstract

Abstract Objective Glucagon-like peptide-1 (GLP-1) plays an emerging role in regulating sodium and water balance. Long-acting GLP-1 receptor agonist (RA) treatment reduces fluid intake and diuresis. In contrast, short-acting GLP-1 RAs induces natriuresis, but its effects on copeptin, a surrogate marker for arginine vasopressin, remain unknown. We therefore investigated the effect of short-acting GLP-1 RAs on copeptin levels. Design This is a secondary analysis of a double-blind, placebo-controlled trial in 13 healthy euvolemic adults. Methods Our primary objective was to investigate the effect of a single 10 µg exenatide injection on copeptin levels. The treatment effect was assessed using the Wilcoxon rank test comparing baseline and 60 minutes post-injection. Results Thirteen healthy participants were included (median age 38 years (IQR, 33-42), 69% male, BMI 26.1 kg/m2 (24.6-29.2)). Copeptin levels were 3.54 pmol/L (2.69-8.53), 4.39 pmol/L (2.69-6.50), and 4.01 pmol/L (2.73-5.74) at baseline, 60, and 90 minutes post- injection, resulting in a mild increase of +0.60 pmol/L, which did not reach statistical significance (95%CI: -0.46-2.07, p=0.23). Excluding participants who experienced nausea (n=3 of 13), the treatment effect was more pronounced (+1.06 pmol/L; 95%CI: -0.06-2.95, p=0.06). Repeated measures correlation revealed a weak non-significant negative correlation between GLP-1-induced decreases in blood glucose and copeptin (r=-0.293, p=0.138). Conclusion This first investigation of a short-acting GLP-1 RA on copeptin suggests a potential modulatory role of GLP-1 on arginine vasopressin regulation, providing preliminary evidence for a direct effect independent of non-osmotic stimuli such as nausea or low glucose levels.

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Cite This Study

Baumann et al. (2026) conducted an RCT in Healthy adults (n=13). Exenatide vs. Placebo was evaluated on Change in copeptin levels from baseline to 60 minutes post-injection (+0.60 pmol/L, 95% CI -0.46-2.07, p=0.23). A single 10 µg exenatide injection in healthy adults produced a non-significant increase in copeptin levels of +0.60 pmol/L at 60 minutes (95% CI -0.46-2.07; p=0.23).

synapsesocial.com/papers/69e9b89b85696592c86ebc53https://doi.org/10.1093/obendo/wjag006
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