TOPLINE:

Treatment with dulaglutide, a GLP-1 receptor agonist, led to a substantial decrease in copeptin levels compared to that with placebo in participants with euvolaemia, independent of changes in blood pressure, BMI, or nausea.

METHODOLOGY:

• Researchers conducted a secondary analysis by pooling data from two cross-over clinical trials to evaluate the effect of dulaglutide on copeptin levels compared with placebo in participants with euvolaemia.
• They analysed data of 54 participants (median age, 27 years; 63% women); of these, 34 had primary polydipsia — defined as a daily fluid intake of more than 3000 mL and a urine output of greater than 50 mL/kg body weight — and 20 were healthy participants.
• All participants received either dulaglutide 1.5 mg or placebo (0.9% sodium chloride) once a week for 3 weeks and attended an 8-hour evaluation visit during the last treatment week following a 12-hour overnight fast.
• The analysis included blood samples for copeptin measurement after each treatment phase; data on serum and urine electrolytes as well as osmolality were evaluated.

TAKEAWAY:

• In the pooled cohort, after 3 weeks, the dulaglutide group showed a significant reduction in copeptin levels compared to the placebo group, with a corresponding median within-subject difference of -0.7 pmol/L (P = .047), indicating a small-to-moderate treatment effect size.
• The reduction in copeptin levels was more pronounced with dulaglutide in men vs women, current smokers vs non-smokers, and those with elevated vs normal systolic blood pressure.
• No significant associations were observed between treatment-induced changes in copeptin levels and GLP-1-mediated outcomes such as a reduction in blood pressure or weight loss.
• Nausea was reported in two healthy participants in the dulaglutide group and was evenly distributed between the dulaglutide and placebo groups in participants with primary polydipsia.

IN PRACTICE:

"Results of our study show that a 3-week treatment with dulaglutide resulted in a significant reduction in copeptin levels, showing an approximate 12% decrease compared to placebo," the authors wrote.

SOURCE:

This study was led by Svenja Leibnitz, Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland. It was published online on January 12, 2026, in the European Journal of Endocrinology.

LIMITATIONS:

The study pooled data from two different study populations consisting primarily of participants with euvolaemia. The baseline comparison of copeptin levels was not performed. Participants with primary polydipsia showed lower copeptin levels under placebo due to excessive daily fluid intake, potentially affecting the treatment effect.

DISCLOSURES:

This study was supported by a grant from the Swiss National Foundation and the University Hospital Basel, Switzerland. One author reported serving on the editorial board of the European Journal of Endocrinology.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.