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

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).