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Effect of glucagon-like peptide-1 receptor agonists on alcohol consumption
Last reviewed: 02.07.2025
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Subgroup analyses suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can reduce alcohol craving and brain reactivity to alcohol stimuli.
In a recent study published in eClinicalMedicine, a team of researchers assessed the association between GLP-1 RAs use and changes in alcohol consumption, as well as their impact on alcohol-related outcomes and brain reactivity to stimuli.
Excessive alcohol consumption is a global health crisis with economic, social and medical impacts. Alcohol use disorders are a leading cause of hospital admissions and deaths. In the United Kingdom (UK), alcohol-related deaths are set to peak in 2022, with economic costs exceeding £21 billion per year.
Existing treatments for alcohol use disorder (AUD) often have limited effectiveness due to poor adherence and side effects. GLP-1 RAs, originally developed to treat type 2 diabetes and obesity, show promise in modulating reward pathways associated with addiction. However, more research is needed to establish their long-term efficacy, safety, and tolerability in the treatment of AUD.
This systematic review followed the PRISMA guidelines and pooled data from previously published studies. An electronic search was conducted on 24 March 2024 in Ovid Medline, EMBASE and PsycINFO databases to identify relevant studies.
Additional resources included grey literature and manual reference screening. An additional search on August 7, 2024, did not identify any new studies. The search was based on the PICO model and refined with expert librarians.
Eligible studies included those who consumed alcohol in moderate to excessive amounts, including AUD. Peer-reviewed articles, published abstracts, and ongoing clinical trials providing sufficient data were included.
Diagnosis of excessive alcohol consumption was made using validated criteria such as the Alcohol Use Disorders Identification Test (AUDIT) and DSM 5 or ICD 10 classifications.
A total of 1,128 records were identified, of which six studies met the inclusion criteria after duplicate removal and screening. These studies included two randomized controlled trials (RCTs), one randomized series, and three retrospective observational studies.
The studies were conducted in Europe, the United States, and India. A total of 88,190 participants were analyzed, including 286 from RCTs and 87,904 from observational studies. Most participants were men (56.9%), with a mean age of 49.6 years. The GLP-1 RAs studied included exenatide, dulaglutide, liraglutide, semaglutide, and tirzepatide.
The interaction between GLP-1 RAs and self-administered measures of alcohol consumption has yielded mixed results. One high-quality RCT found no significant reduction in alcohol consumption after exenatide treatment.
However, a secondary analysis of another high-quality RCT showed a 29% reduction in weekly alcohol consumption with dulaglutide compared with placebo, although this effect was not observed in heavy drinkers.
A prospective cohort study found significant reductions in the number of drinks and binge drinking episodes with semaglutide and tirzepatide compared with the control group. Observational studies have shown reductions in alcohol consumption and AUD rates with liraglutide and semaglutide, although these data were rated as lower-quality evidence.
In subgroup analyses, exenatide showed a significant reduction in heavy drinking days and alcohol consumption in participants with a body mass index (BMI) >30 kg/m². In contrast, in participants with a BMI <25 kg/m², exenatide increased heavy drinking days compared with placebo.
Additionally, an analysis of healthcare data showed that GLP-1 RAs were associated with fewer alcohol-related medical events in the first three months of treatment. However, this effect was not maintained with longer treatment.
Functional brain imaging has provided insight into the possible effects of GLP-1 RAs on the central nervous system. Exenatide significantly reduced cue reactivity in addiction-related brain regions and dopamine transporter availability in the striatum, suggesting a role in modulating reward pathways and working memory. However, these effects did not correlate with significant changes in subjective alcohol craving.
Side effects were primarily gastrointestinal, including nausea, vomiting, and diarrhea. Other reported side effects included respiratory infections, injection site reactions, and depressed mood.
The quality assessment categorised two studies as high quality, two as moderate, and two as low quality, with the main concerns being inconsistent reporting and bias.
Overall, this systematic review examined the effects of GLP-1 RAs on alcohol consumption in heavy drinkers, analyzing six studies, including two RCTs.
Although observational studies have shown reductions in alcohol consumption, RCTs have produced inconsistent results, particularly in obese individuals. Mechanistic studies have suggested that GLP-1 RAs may affect pathways in the brain associated with addiction, but evidence has been limited. Adverse effects have been primarily gastrointestinal, with limited long-term safety data.