GLP-1 Receptor Agonists

Elisabet Jerlhag
Endocrinology, Volume 166, Issue 4, April 2025, bqaf028
https://doi.org/10.1210/endocr/bqaf028

Abstract

Glucagon-like peptide-1 (GLP-1) is abundant in the circulation, and it is well-known to regulate glucose homeostasis, feeding, and body weight. GLP-1 receptor agonists are therefore approved for treating type 2 diabetes and obesity. However, more recent research has demonstrated that GLP-1 acts within the brain to modulate reward responses, thereby highlighting GLP-1 as a potential target for addiction. Specifically, preclinical studies demonstrated that GLP-1 receptor agonists decrease alcohol intake, reduce the motivation to consume alcohol, and prevent relapse drinking by potentially lowering alcohol-induced reward. These preclinical results have been confirmed and extended in human studies in which GLP-1 receptor agonists reduce alcohol intake in patients with alcohol use disorder (AUD) who have a regular weight or comorbidity of obesity or type 2 diabetes. On a similar note, genetic variations in genes encoding for the GLP-1 receptor are associated with AUD and heavy drinking. The central mechanisms by which GLP-1 regulates alcohol-related behaviors are not fully defined, but may involve areas central to reward as well as regions projecting to these reward areas, such as the nucleus tractus solitarius of the brainstem. Together, existing preclinical and clinical data suggest that GLP-1 is involved in the AUD process and implies its role as a tentative treatment for AUD.

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