KEY TAKEAWAY: Investigates the dual therapeutic efficacy of glucagon-like peptide-1 receptor agonists in reducing nicotine cravings and controlling post-cessation weight gain. Results suggest GLP-1 receptor modulation attenuates central reward pathways associated with nicotine addiction while simultaneously mitigating metabolic side effects.
Abstract
Introduction
Smoking and obesity are leading risk factors for morbidity and mortality worldwide. Recent studies have demonstrated the efficacy of glucagonlike peptide-1 (GLP-1) receptor agonists in reducing weight and improving metabolic outcomes. Emerging evidence suggests that these agents may also influence reward-related pathways, offering potential benefit for nicotine addiction and mitigating post-cessation weight gain. This study aimed to evaluate the efficacy of GLP-1 receptor agonists for smoking cessation and their effects on post-cessation weight and BMI.
Methods
A systematic review and meta-analysis of randomized controlled trials was conducted, with the literature searched through November 2025 in PubMed, Scopus, the Cochrane Library, and Web of Science. Eligible studies included adult smokers (Population) receiving GLP-1 receptor agonists (Intervention) compared with placebo or standard care (Comparator), reporting smoking cessation and/ or post-cessation weight or BMI outcomes (Outcomes). Random-effects models were used to pool data, with odds ratios (ORs) for abstinence and weighted mean differences (WMDs) for weight and BMI, and heterogeneity assessed using the I2 statistic.
Results
Of the 751 records screened, 26 full texts were reviewed, and two randomized controlled trials (n=337) were included. Compared with placebo, GLP-1 receptor agonists showed no significant effect on smoking cessation (OR=1.36; 95% CI: 0.55–3.35, p=0.51; I2=66.93%; very low certainty), but significantly reduced post-cessation body weight (WMD=4.14 kg, 95% CI: -7.22 – -1.05, p=0.01; I2=19.93%; low certainty) and BMI (WMD= -1.77 kg/m2, 95% CI: -2.20 – -1.34, p=0.00; I2=00.0%; low certainty).
Conclusion
While GLP-1 receptor agonists have revolutionized the treatment of diabetes and obesity, their role in smoking cessation remains inconclusive. However, reductions in post-cessation weight and BMI highlight their potential as adjunctive agents to address weight-related relapse risk. Larger, longer duration trials with newer GLP-1 agents are warranted to confirm these findings and clarify their role in smoking cessation.