Repurposing incretin-based therapies for alcohol use disorder: a systematic review of efficacy and safety relative to standard pharmacotherapies in a recent comparative context
Aristomenis G. Alevizopoulos, Vasileios Vasilakos, Iakovos Kritikos, Maria Alevizopoulou, Eleni Korompoki, Theodora Psaltopoulou, Stavroula A. PaschouBackground:
Alcohol use disorder (AUD) affects millions worldwide, but current treatments, such as disulfiram, naltrexone, acamprosate, and topiramate, have limitations in efficacy and tolerability. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), commonly used for diabetes and obesity, may offer a new approach by targeting brain pathways involved in alcohol cravings.
Objectives:
This review aims to systematically evaluate the preliminary efficacy and safety of GLP-1 RAs and other incretin-based therapies in treating AUD within a recent comparative context, alongside standard pharmacotherapies.
Design:
Systematic review.
Data sources and methods:
A comprehensive literature review was conducted by searching the PubMed/Medline, Web of Science, and Scopus databases from February through June 2025. The studies included were either randomized controlled trials (RCTs) or observational studies, written in English. Studies were selected based on their evaluation of GLP-1 RAs or comparator drugs in reducing alcohol consumption or related outcomes in patients with AUD.
Results:
The selected 12 studies correspond to a population of 95,004 participants, but only 663 were from RCTs, while the majority were from a single registry cohort. Emerging data suggest GLP-1 RAs may reduce heavy drinking days, particularly in individuals with a higher BMI. Furthermore, observational analyses indicate a potential association between GLP-1 RA use and reduced alcohol-related hospitalizations, while metabolic data suggest biologically plausible, albeit unconfirmed, hepatoprotective effects.
Conclusion:
While the large, aggregated sample size highlights the therapeutic promise of GLP-1 RAs for AUD, particularly for patients with metabolic comorbidities, the heavy reliance on observational data precludes claims of clinical equivalence with established pharmacotherapies. Appropriately powered, dedicated RCTs are required to confirm direct efficacy and long-term safety.
Trial registration:
Not registered.