Impact of glucagon-like peptide-1 receptor agonists on alcohol consumption: A systematic review

Subgroup analyses reveal GLP-1 RAs may reduce alcohol cravings and brain cue reactivity.

Study: Association between glucagon-like peptide-1 receptor agonists use and change in alcohol consumption: a systematic review. Image Credit: Kmpzzz/Shutterstock.com

In a recent study published in the eClinicalMedicine, a group of researchers assessed the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and changes in alcohol consumption, along with their impact on alcohol-related outcomes and brain cue reactivity.

Background

Excessive alcohol consumption is a global health crisis, economic, driving social, and medical burdens, with alcohol-related disorders being a leading cause of hospitalizations and deaths. In the United Kingdom (UK) alone, alcohol-related deaths peaked in 2022, and the economic impact exceeds £21 billion annually.

Existing treatments for alcohol use disorder (AUD) often have limited efficacy due to poor adherence and adverse effects. GLP-1 RAs, originally developed for type 2 diabetes and obesity, show promise in modulating reward pathways central to addiction. Further research is needed to establish their long-term efficacy, safety, and tolerability in managing AUD.

About the study  

This systematic review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and synthesized existing data from previously published studies. An electronic search was conducted on March 24, 2024, across Ovid Medline, EMBASE, and PsycINFO to identify relevant studies from inception to the search date.

Additional resources, including grey literature and manual screening of references, were also explored. A supplementary search on August 7, 2024, yielded no new studies. The search strategy was based on the Population, Intervention, Comparator, and Outcome (PICO) model and refined with expert librarian input.

Eligible studies included those involving individuals with occasional or excessive alcohol consumption, including AUD. Peer-reviewed journal articles, published abstracts, and ongoing clinical trials providing sufficient data were included.

Diagnosis of excessive alcohol consumption was identified through validated criteria, including Alcohol Use Disorders Identification Test (AUDIT) scores and Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) or International Classification of Diseases 10 (ICD 10) classifications.

Titles and abstracts were independently screened by reviewers using systematic review software, and data extraction followed a structured template.

The primary outcome assessed was the impact of GLP-1 RAs on alcohol intake. Secondary outcomes included healthcare utilization, alcohol-related health events, and adverse events.

Study results

A total of 1,128 records were initially identified, with six studies meeting the eligibility criteria after duplicates were removed and screening was conducted. These studies included two randomized controlled trials (RCTs), one case series, and three retrospective observational studies.

The included studies originated from Europe, the United States, and India. In total, 88,190 participants were analyzed, including 286 from RCTs and 87,904 from observational studies. The majority were male (56.9%), with a pooled mean age of 49.6 years. GLP-1 receptor agonists (GLP-1 RAs) studied included exenatide, dulaglutide, liraglutide, semaglutide, and tirzepatide.

The interaction between GLP-1 RAs and self-reported alcohol measures showed mixed results. One high-quality RCT found no significant reduction in self-reported alcohol consumption after exenatide treatment.

However, a secondary analysis of another high-quality RCT reported a 29% reduction in weekly alcohol intake with dulaglutide compared to placebo, though 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 to controls. Observational studies reported reductions in drinking and AUD-related scores with liraglutide and semaglutide, though these were assessed as lower-quality evidence.

In subgroup analyses, exenatide showed significant reductions in heavy drinking days and alcohol intake in participants with a body mass index (BMI) >30 kg/m². Conversely, in participants with a BMI <25 kg/m², exenatide increased heavy drinking days compared to placebo.

Additionally, an analysis of healthcare data revealed that GLP-1 RAs were associated with fewer alcohol-related health events in the initial three months of treatment. However, this effect did not persist with longer treatment durations.

Functional brain imaging provided insight into the potential central nervous system effects of GLP-1 RAs. 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.

Adverse events were primarily gastrointestinal and included nausea, vomiting, and diarrhea. Other reported side effects included respiratory infections, injection site reactions, and depressive mood.

Quality assessment categorized two studies as high-quality, two as medium, and two as low-quality, with concerns primarily related to inconsistent reporting and bias.

Conclusions

To summarize, this systematic review explored the impact of GLP-1 Ras on alcohol consumption in individuals with excessive drinking, analyzing six studies, including two RCTs.

While observational studies suggested reductions in alcohol use, RCTs showed inconsistent effects, particularly in individuals with obesity. Mechanistic studies indicated GLP-1 RAs might influence addiction-related brain pathways, though the evidence was limited. Adverse events were mainly gastrointestinal, with insufficient data on long-term safety.