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Randomized Controlled Trial
. 2025 May;49(5):1161-1165.
doi: 10.1111/acer.70041. Epub 2025 Mar 23.

Blood phosphatidylethanol measurements indicate GLP-1 receptor stimulation causes delayed decreases in alcohol consumption

Mathias E Jensen  1 , Mette K Klausen  1 , Marianne L Bergmann  2 , Gitte M Knudsen  3   4 , Tina Vilsbøll  4   5 , Christophe Stove  6 , Anders Fink-Jensen  1   4
Affiliations
Randomized Controlled Trial

Blood phosphatidylethanol measurements indicate GLP-1 receptor stimulation causes delayed decreases in alcohol consumption

Mathias E Jensen et al. Alcohol Clin Exp Res (Hoboken). 2025 May.

Abstract

Background: The investigation of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) as a potential treatment for individuals with alcohol use disorder (AUD) and obesity is currently underway. In this secondary analysis of a randomized placebo-controlled trial, we included AUD patients with comorbid obesity and assessed the effect of the GLP-1RA exenatide versus placebo on alcohol consumption as measured by the alcohol biomarker phosphatidylethanol (PEth).

Methods: Thirty AUD patients (9 females, 21 males), with an average age of 53 years and a body mass index (BMI) of at least 30 kg/m2, were included in this secondary analysis. Blood samples for PEth were collected at baseline and at weeks 4, 12, 20, and 26. The effect of time and treatment on PEth levels was analyzed using a baseline-adjusted linear mixed model.

Results: A significant interaction between time and treatment was observed at Week 26, with PEth levels reduced by -0.9 μmol/L in the exenatide group compared to placebo (95% CI [-1.6 to -0.1], p = 0.03). However, the difference in PEth blood levels between the exenatide and placebo groups was not significant at earlier time points.

Conclusion: This secondary analysis indicates that exenatide has a delayed yet significant impact on alcohol consumption in individuals with AUD and obesity, as assessed by PEth levels. These findings warrant further investigation, which is currently underway (NCT05895643).

Keywords: GLP‐1 receptor agonist; PEth; alcohol biomarkers; alcohol use disorder; phosphatidylethanol.

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Conflict of interest statement

Tina Vilsbøll has, over the recent three years, served on scientific advisory panels, been part of speaker's bureaus, and served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GSK, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. The other authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
The effect of time and treatment (exenatide vs. placebo) on PEth levels in individuals with AUD and obesity. Data are presented as means (SEM). PEth, phosphatidylethanol.
FIGURE 2
FIGURE 2
Blood levels of PEth versus percentage of heavy drinking days the past 30 days, assessed at baseline, Week 4, Week 12, Week 20, and Week 26 (end of the trial). PEth levels and self‐reports of alcohol consumption were significantly correlated at all assessment time points except Week 12: Baseline, ρ(30) = 0.6, p = 0.01, Week 4, ρ(27) = 0.6, p = 0.02, Week 12, ρ(21) = 0.4, p = 0.13, Week 20, ρ(14) = 0.8, p = 0.01, and Week 26, ρ(18) = 0.7, p = 0.01. Dashed lines represent regression lines with confidence bands (gray). PEth, phosphatidylethanol.
See this image and copyright information in PMC

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