Association between glucagon-like peptide-1 receptor agonists use and change in alcohol consumption: a systematic review

Background: Despite the availability of various pharmacological and behavioural interventions, alcohol-related mortality is rising. This systematic review aimed to critically evaluate the existing literature on the association between glucagon-like peptide-1 receptor agonists use (GLP-1 RAs) and alcohol consumption. Methods: Electronic searches were conducted on Ovid Medline, EMBASE, PsycINFO, clintrials.gov, and ProQuest until the end of March 2024. An updated search was done on 7th of August 2024. The primary outcome was to explore the association between GLP-1 RAs use and change in alcohol consumption. Secondary outcomes included evaluating the impact of GLP-1 RAs on occurrences of alcohol-related events, healthcare utilisation, and the effect on functional magnetic resonance imaging (fMRI) cue reactivity. This study is registered with PROSPERO #CRD42024531982. Findings: Six studies totalling 88,190 participants were included with 38,740 (43.9%) receiving GLP-1 RA, but only 286 participated in randomised controlled trials. Pooled mean age was 49.6 years (SD = 10.5). RCT data did not show a reduction in alcohol consumption over 30 days after 24 weeks of treatment with exenatide versus placebo (heavy drinking days 6.0 [higher in control group], 95% CI −7.4 to 19.4, p = 0.37), a subgroup analysis found a positive effect in people with obesity (BMI >30 kg/m²), with significant reductions in brain reward centre cue reactivity on fMRI. In a secondary analysis of an RCT participants taking dulaglutide compared to placebo were 29% more likely to reduce alcohol intake (relative effect size 0.71, 95% CI 0.52–0.97, p = 0.04). Observational studies showed fewer alcohol-related healthcare events and a significant reduction in alcohol use with GLP-1 RAs treatment compared to DPP4-Dipeptidyl peptidase 4 use, no treatment and/or alcohol intake at baseline. Interpretation: There is little high-quality evidence demonstrating the effect of GLP-1 RAs on alcohol use. Subgroup analysis from two RCTs and supporting data from four observational studies suggest that GLP-1 RAs may reduce alcohol consumption and improve outcomes in some individuals. Heterogeneous study findings warrant further research to establish the effectiveness and safety of GLP-1 RAs in this population. Funding: National Institute for Health and Care Research (NIHR): Award-ID: NIHR155469; NIHR154191; NIHR155530. NIHR Nottingham Biomedical Research Centre, Award-ID: BRC-1215-20003.