Trial results for a Phase 2 study (NCT05530577) investigating semaglutide for tobacco use disorder and nicotine addiction were posted on ClinicalTrials.gov on 2025-07-18. The study observed a mean reduction in nicotine self-administration of 0.8 cigarettes in the semaglutide group compared to 0.5 cigarettes in the sham/placebo group.
Background
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. Tobacco use disorder and nicotine addiction represent a major public health challenge, being the foremost cause of preventable deaths. Preclinical studies have suggested that GLP-1 receptor agonists may reduce the intake and/or reinstatement of addictive drugs, including nicotine, prompting this translational research.
Trial design
The study (NCT05530577), titled "Effects of Semaglutide on Nicotine Intake," was a Phase 2, completed trial that enrolled 24 participants. The trial investigated semaglutide in individuals with tobacco use disorder and nicotine addiction. Participants received either semaglutide or sham/placebo.
Key results
The trial evaluated several key measurements related to nicotine intake and smoking behavior:
- For "Change in Nicotine Self-Administration":
- The semaglutide group showed a mean change of -0.8 cigarettes (Standard Deviation: 0.63).
- The sham/placebo group showed a mean change of -0.5 cigarettes (Standard Deviation: 0.69).
- For "Change in Nicotine Reinstatement Duration":
- The semaglutide group showed a mean change of 10.3 minutes (Standard Deviation: 27.6).
- The sham/placebo group showed a mean change of -2.2 minutes (Standard Deviation: 20.1).
- For "Change in Daily Cigarette Smoking":
- The semaglutide group showed a mean change of -3.35 cigarettes per day (Standard Deviation: 5.25).
- The sham/placebo group showed a mean change of -2.27 cigarettes per day (Standard Deviation: 4.15).
What this means
These preliminary Phase 2 results for semaglutide in nicotine addiction are mixed. While numerically greater reductions in nicotine self-administration and daily smoking were observed with semaglutide compared to sham/placebo, an increase in nicotine reinstatement duration was also seen. Due to the small enrollment of 24 participants and the lack of statistical analyses, further larger studies are necessary to establish the clinical significance and efficacy of semaglutide for tobacco use disorder and nicotine addiction.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05530577, titled "Effects of Semaglutide on Nicotine Intake," were posted on 2025-07-18 on clinicaltrials.gov.