GLP-1 Receptor Agonists (GLP-1RAs) for treatment of tobacco and alcohol dependence: a systematic review and meta-analysis of randomised controlled trials
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Background
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) might reduce tobacco and alcohol use. We synthesised evidence from randomised controlled trials (RCTs) on smoking and alcohol outcomes, including secondary outcomes reported in trials conducted for other clinical purposes.
Methods
We searched MEDLINE, Embase, PsycINFO, Web of Science, CENTRAL, PubMed, and registries for RCTs comparing GLP-1RAs with placebo from inception to August 18, 2026. Smoking and alcohol outcomes were synthesised using random-effects meta-analyses. We assessed risk of bias (RoB) with RoB-2, and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Findings
Fourteen trials involving 1149 participants were included; 13 contributed to meta-analyses. Across the 14 trials, 8 recruited participants not seeking either tobacco or alcohol treatment. The other 6 recruited treatment-seeking participants: 3 for tobacco and 3 for alcohol. Eight trials reported smoking-related outcomes, 11 reported alcohol outcomes, and 5 reported both. Follow-up ranged from 6 to 60 weeks.
All 4 pooled smoking-related estimates favoured GLP-1RAs, although all 95% CIs included no difference and were compatible with increases and decreases in outcomes; e.g., smoking cessation, OR 1.39 (95% CI, 0.77 to 2.53, k=3). Restricting analyses to semaglutide trials indicated a reduction in cigarettes per day (CPD) (standardised mean difference [SMD]=-0.10, 95%CI:-0.16 to -0.04; k=3).
Across agents, pooled estimates favoured GLP-1RAs for days without alcohol (SMD=0.35, 95%CI: 0.12 to 0.59, k=3). Pooled estimates of semaglutide-only trials also favoured treatment for alcohol consumption (grams/day; SMD=-0.56, 95%CI:-0.82 to -0.30; k=2), craving (SMD=-0.60, 95%CI:-0.91 to -0.29; k=2), drinks per drinking day (SMD=-0.59, 95%CI:-0.86 to -0.32; k=3), drinks per calendar day (SMD=-0.48, 95%CI:-0.87 to -0.09; k=2) and heavy drinking days (SMD=-0.45, 95%CI:-0.85 to -0.06; k=3), and alcohol-free days (SMD=0.41, 95%CI:0.09 to 0.73; k=2).
Two of 41 assessed results were at low RoB, 31 raised some concerns and 8 were at high risk; certainty was moderate for 1 outcome, low for 4 and very low for 8.
Interpretation
GLP-1RAs may reduce alcohol consumption and CPD, with the clearest evidence for semaglutide. These findings should be contextualised by most evidence being low- to very-low-certainty. Larger trials are needed to establish clinically meaningful benefit and sustained abstinence.
KEY POINTS
Question
Do glucagon-like peptide-1 receptor agonists improve smoking and alcohol outcomes compared with placebo?
Findings
This systematic review included 14 randomised trials involving 1149 participants, with 13 trials contributing to meta-analyses. Alcohol-free days increased significantly across agents, and semaglutide analyses indicated significant reductions in alcohol consumption; and cigarettes per day. There was insufficient evidence on smoking-cessation result.
Meaning
GLP-1 receptor agonists show potential for reducing alcohol consumption, and cigarettes per day, but predominantly low or very low certainty evidence warrants larger trials before their role in addiction treatment can be established.
