A Systematic Review and Meta-Analysis Evaluating the Role of GLP-1 Receptor Agonists in Substance Use Disorders.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 42524101 · doi:10.7759/cureus.111641
What was done
Authors conducted a systematic review and random-effects meta-analysis of parallel-group or crossover randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists versus placebo or control in adults with substance use disorders. Databases and trial registries were searched through April 30, 2026. Measured outcomes included days without alcohol consumption, cigarettes smoked per day (CPD), and Fagerström Test for Nicotine Dependence (FTND) scores. Study quality was evaluated using Cochrane RoB 2 and GRADE.
What was found
Five RCTs were included with 764 total participants (follow-up 6 to 52 weeks; three trials for alcohol, four for tobacco). Meta-analysis demonstrated no statistically significant effects on days without alcohol consumption (MD -1.96 days, 95% CI -17.97 to 14.05; I² = 74%), cigarettes smoked per day (MD -0.55, 95% CI -1.76 to 0.65; I² = 45%), or FTND scores (MD 0.02, 95% CI -0.32 to 0.36; I² = 0%). RoB 2 rated three trials as low risk and two with some concerns; GRADE certainty ranged from low to moderate.
Why it matters
Despite preclinical evidence suggesting GLP-1 modulates reward pathways, current pooled randomized human trials do not show benefit for alcohol or tobacco cessation.
Limits
The analysis is constrained by a small number of trials (n = 5) and participants (n = 764), resulting in wide confidence intervals. Heterogeneity was high for alcohol outcomes (I² = 74%), two trials had risk-of-bias concerns, and evidence was limited to alcohol and nicotine without data on other substance use disorders.
Cited by
- context GLP-1 receptor agonists reduce desire in reward pathways, with emerging evidence showing decreased cravings for addictive behaviors such as gambling, shopping, alcohol, and smoking.