A pilot trial found the GLP-1 drug exenatide worked best for smoking cessation in heavy smokers without obesity or depression who carry a specific nicotine receptor gene variant.
94.4% probabilityBayesian analysis showed 94.4% probability that exenatide is more effective than placebo for smoking cessation in participants without obesity
What the researchers found
In a secondary analysis of a pilot RCT, the GLP-1 agonist exenatide showed stronger smoking cessation benefits in specific patient subgroups. Exenatide (added to nicotine patch) worked better than placebo plus nicotine patch in people who smoked more than 20 cigarettes per day (posterior probability 81.7%), those without obesity (PP = 94.4%), those without prediabetes (PP = 76.0%), and those with no or minimal depression (PP = 91.2%).
A striking genetic finding emerged: exenatide was more effective only in individuals with the CHRNA rs16969968 GG genotype (PP = 88.6%), a nicotine receptor gene variant associated with smoking behavior. This suggests that GLP-1 drugs for smoking cessation may be most effective in a specific subset of smokers — heavy smokers who are not obese, not depressed, and carry a particular genetic profile.
Why it matters
The idea that GLP-1 drugs could help people quit smoking is one of the most exciting emerging applications of these peptides. But not everyone may benefit equally. This study is among the first to identify who responds best to GLP-1 treatment for smoking cessation, potentially enabling precision medicine approaches. The finding that metabolic health, depression status, and genetics all predict response suggests the mechanism involves more than just appetite suppression.
The numbers in context
n=84 · Exenatide 2 mg SC once weekly + nicotine patch 21 mg · Stronger in >20 cig/day (PP=81.7%) · Stronger without obesity (PP=94.4%) · Only effective with minimal depression (PP=91.2%) · CHRNA rs16969968 GG genotype (PP=88.6%)
How the study worked
Secondary analysis of a randomized, placebo-controlled pilot trial. 84 smokers with prediabetes and/or overweight were randomized 1:1 to once-weekly exenatide 2 mg or placebo, both with nicotine patch (21 mg) and counseling. The primary outcome was biologically confirmed 7-day point prevalence abstinence at week 6. Bayesian generalized linear modeling was used to explore how baseline demographics, clinical factors, smoking intensity, psychosocial measures, and genetic variants moderated treatment response.
Who was studied
Adult smokers with prediabetes and/or overweight/obesity
What this study cannot tell us
This is a secondary (post-hoc) analysis of a small pilot trial with only 84 participants — subgroup analyses with this sample size should be considered hypothesis-generating, not definitive. Bayesian posterior probabilities ≥75% were used as thresholds, which is less stringent than conventional significance testing. Multiple subgroup comparisons increase the risk of finding spurious associations. The parent trial used exenatide (an older GLP-1 agonist), not semaglutide or tirzepatide.
How to read the evidence
This is a well-designed secondary analysis of a randomized controlled trial published in a leading tobacco research journal. However, the small sample size (n=84) and post-hoc nature of the subgroup analyses mean findings should be considered preliminary and hypothesis-generating.
When this study was published
Published in 2025. Highly current research at the frontier of GLP-1 applications for addictive behavior, with the parent trial being one of the first RCTs of GLP-1 agonists for smoking cessation.
The bigger picture
GLP-1 agonists are increasingly linked to reduced addictive behaviors — from alcohol to smoking to compulsive eating. This study moves the field toward precision by identifying which smokers are most likely to benefit. If confirmed in larger trials, genetic testing and clinical profiling could guide who gets prescribed GLP-1 drugs for smoking cessation, mirroring the precision medicine revolution in cancer treatment.
Questions still open
- Would newer, more potent GLP-1 agonists like semaglutide show even stronger smoking cessation effects in these responder subgroups?
- Why does exenatide work better in non-obese smokers — does the mechanism differ from its weight-loss effects?
- Could the CHRNA rs16969968 genotype become a clinical biomarker for prescribing GLP-1 drugs for smoking cessation?
Common questions
Can GLP-1 drugs like Ozempic help you quit smoking?
Why would a diabetes drug help with smoking?
Read the original research
Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 27(7), 1294-1300
Citation
Yammine, Luba; de Dios, Constanza; Suchting, Robert; Green, Charles E; Nielsen, David A; Walss-Bass, Consuelo; Schmitz, Joy M. (2025). Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation.. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 27(7), 1294-1300. https://doi.org/10.1093/ntr/ntaf005