GLP-1 receptor agonists for smoking cessation: a narrative review of weight management potential

Smoking cessation is a major public health goal, yet concerns about post-cessation weight gain remain a significant barrier for many smokers. The metabolic and behavioral changes following nicotine withdrawal frequently lead to increased caloric intake and reduced energy expenditure, potentially triggering relapse. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for type 2 diabetes and later approved for weight management, have recently been investigated as a potential strategy to address both nicotine dependence and weight control. Emerging evidence from preclinical studies and limited clinical trials suggests that GLP-1 RAs may reduce nicotine cravings and intake by modulating central reward pathways while simultaneously curbing appetite and supporting weight loss. This dual mechanism may improve quit success rates and mitigate the psychological burden of post-cessation weight gain. However, the current human evidence base is limited, with small sample sizes, short follow-up periods, and reliance on preliminary data. While the pharmacological profile and cardiometabolic benefits of GLP-1 RAs make them a promising candidate for adjunctive use in smoking cessation, more rigorous randomized controlled trials are required to confirm efficacy, evaluate safety, and establish clinical guidelines. This narrative review synthesizes existing evidence to highlight both the potential and the current uncertainties surrounding GLP-1 RAs as dual-target pharmacotherapy for smoking cessation and weight management.