Introduction
Alcohol use disorder (AUD) remains a significant global health concern. Despite the availability of various pharmacological and behavioural interventions, alcohol-related mortality is rising.
Aims & Methods
This systematic review aimed to critically evaluate the existing literature on the role of glucagon-like peptide receptor 1 analogues (GLP-1 RAs) in people with AUD.
Electronic search was conducted on Ovid Medline, EMBASE, Cochrane Central and PsycINFO from inception to March 2024. Grey literature was searched. The primary outcome of the review was to explore the impact of GLP-1 RAs on self-reported alcohol intake in people with AUD. The extracted data were organized and synthesized to identify key findings and trends evaluating the potential impact of GLP-1 RAs on alcohol consumption in AUD. Narrative synthesis was done to provide a coherent and detailed narrative of the evidence, highlighting significant findings, relationships, and implications. PROSPERO (CRD42024531982).
Results
Seven studies comprising 88,163 participants were included; of these, 38,746 (43.9%) were treated with GLP-1 RAs. Pooled mean age was 49.6 years (SD=10.5), 56.9% (n=50,151/88157) were male, and if the study provided ethnicity 87.5 % (n=426/487) were white. An RCT comparing exenatide with placebo found no significant difference in self-reported alcohol measures at 26 weeks (percentage point reduction: heavy drink days: 6.0, 95% CI -7.4 to 19.4, p=0.37; total alcohol consumption: -42.0 g/30 days, 95% CI -507.7 to 423.7, p=0.86; days without alcohol use: -10.5, 95% CI -2.6 to 23.4, p=0.11). But in participants (n=30) with BMI > 30 kg/m², exenatide compared with placebo was associated with a significant reduction in heavy drinking days (percentage point reduction 23.6, 95% CI, –44.4 to –2.7, P=0.034) and in total alcohol consumed (-1,205 g, 95% CI, –2,206 to –204, P= 0.026). Another RCT showed dulaglutide users compared to placebo were 29% more likely to reduce weekly alcohol consumption (relative effect size: 0.71, p=0.04). In an observational study, authors reported with liraglutide (n=42) 21.4% stopped and 78.6% reduced drinking (p<0.05). A prospective cohort control study showed people on semaglutide or tirzepatide (n=153) compared to no medication significantly reduced number of alcoholic drinks consumed and binge drinking (p<0.05). In a case series (n=6) semaglutide use was associated with a 9.5-point reduction in alcohol use disorder identification test score. A population-based study from Denmark (n=87,676) reported that at 90 days people on GLP-1 RAs compared to one on dipeptidyl peptidase-4 inhibitors (DPP-4) were less likely to experience alcohol-related events ( HR 0. 46, 95% CI 0.24 to 0.86) and effect remained positive long term (356-4619 days: HR 0.72, 95% CI 0.60–0.86). Two qualitative studies examining Reddit social media posts from people on GLP-1 RAs noted over two-thirds addressed a reduction in alcohol consumption. Functional brain imaging suggested significant reductions in cue reactivity were observed in the ventral striatum [F(1,31) = 4.744, P = 0.037, partial η2 = 0.133], dorsal striatum [F(1,31) = 6.124, P = 0.019, partial η2 = 0.165], and putamen [F(1,31) = 4.730, P = 0.037, partial η2 = 0.132] after 26 weeks of exenatide treatment compared with placebo (Table 1). Two studies were of high quality, two medium, and three low.
Conclusion
GLP-1 RAs show promise in reducing alcohol consumption and improving outcomes in individuals with AUD, although heterogeneous study findings warrant further research to establish true effectiveness and safety of GLP-1 RAs in AUD.
References
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