Title : GLP-1 receptor agonists for smoking cessation: A systematic review and meta-analysis of randomized controlled trials
Abstract:
Introduction: Cigarette smoking remains the leading cause of preventable disease, disability and death in the US, yet sustained abstinence is undermined by high relapse rates, whereas post-cessation weight gain is one of the most concerns of relapse. Glucagon?like peptide?1 Receptor Agonists (GLP?1RA), widely used in metabolic disease, are emerging as adjunct treatment for substance use disorders. GLP?1 receptors in the ventral tegmental area and nucleus accumbens modulate mesolimbic dopamine signaling, attenuating reward valuation and cue?reactivity, while, peripherically, reduce appetite and improve glycemic control—addressing, thus, metabolic drivers of relapse. Hence, randomized trials are evaluating GLP?1RA for nicotine, alcohol, and stimulant use. In this way, this review assesses GLP?1RA–based strategies to enhance smoking cessation efficacy and durability.
Methods: We systematically searched Pubmed/MEDLINE, PsycINFO and Cochrane Library, in July, 2025, for published Randomized Controlled Trials (RCTs). Statistical analyses were performed using R software v. 4.5.1, and we used risk ratio (RR), mean difference (MD) and 95% confidence intervals (CI). Outcomes assessed were abstinence rates and post-cessation weight gain.
Results: Out of 425 database records, three randomized trials including 410 patients were eligible; 207 (50.5%) received GLP?1RA. The treatment duration ranged from 6 to 26 weeks. Compared with placebo, GLP-1RAs significantly reduced post-cessation body weight (MD –2.59 kg; 95% CI –3.70 to –1.48; P < 0.001). No difference was observed in abstinence rates during the treatment period (RR 1.11; 95% CI 0.82 to 1.50; P = 0.512) or during the post-treatment follow-up (RR 1.04; 95% CI 0.75 to 1.45; P = 0.806).
Conclusion: GLP?1RA is a safe adjunctive therapy for smoking cessation by effectively mitigating post?cessation weight gain. While pooled evidence suggests consistent benefits in weight management across included trials, heterogeneity in patient characteristics and intervention protocols limits generalizability. More RCTs with stratified analyses by baseline metabolic status and extended follow?up are needed to establish efficacy across diverse patient subgroups.
