Semaglutide Shows Early Potential in Reducing Nicotine Craving in Daily Smokers: Randomized Trial
USA: A phase 2a randomized clinical trial published in JAMA Network Open suggests that once-weekly semaglutide may help reduce cigarette craving and body weight in adults who smoke daily, even among individuals not actively trying to quit smoking.
The study was led by Christian S. Hendershot from the Department of Population and Public Health Sciences at the Keck School of Medicine of the University of Southern California.
Smoking remains a major global health burden and a leading cause of premature death, largely due to its strong association with cardiovascular and metabolic diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used in the management of obesity and diabetes, have recently shown early signals of potential benefit in reducing addictive behaviours, including nicotine use.
To examine this, researchers conducted a parallel-arm randomized clinical trial in adults who smoked at least five cigarettes daily but were not actively seeking smoking cessation. The study was conducted at an academic medical centre between October 2022 and April 2024.
Participants were randomly assigned to receive either once-weekly subcutaneous semaglutide or placebo for nine weeks, with doses gradually increased from 0.25 mg to 1.0 mg. The study evaluated multiple outcomes, including cigarette consumption, nicotine craving, smoking resistance, body weight, and metabolic markers, assessed through laboratory testing and weekly follow-ups.
A total of 45 participants were enrolled, with 24 randomized equally between the semaglutide and placebo groups. The mean age was 44 years, and most participants were women. At baseline, participants reported an average consumption of about 15 cigarettes per day.
The trial revealed the following findings:
- Primary analyses showed no significant differences between the semaglutide and placebo groups in laboratory measures of smoking resistance or the number of cigarettes smoked during testing sessions.
- Additional change-score analyses demonstrated greater reductions in laboratory cigarette smoking among participants receiving semaglutide compared with placebo after treatment.
- Semaglutide treatment was associated with significantly lower weekly cigarette craving throughout the study period.
- Participants receiving semaglutide experienced meaningful reductions in body weight relative to placebo.
- Hemoglobin A1c levels were also reduced in the semaglutide group compared with the placebo group.
- Exploratory analyses suggested that semaglutide may help reduce nicotine withdrawal symptoms.
Semaglutide did not lead to a significant reduction in daily cigarette use during the trial. The researchers emphasized that the study was an early-phase screening trial with a small sample size and limited follow-up, which restricts the robustness and generalisability of the findings.
The authors called for larger, long-term studies to better assess the efficacy and safety of GLP-1–based therapies in smoking-related outcomes, including cessation and cardiometabolic benefits. They also emphasized evaluating these drugs in real-world smokers using them for obesity or diabetes rather than for smoking cessation.
They suggested that GLP-1 therapies may offer dual benefits by reducing nicotine craving and improving cardiometabolic risk factors such as obesity, diabetes, and cardiovascular disease. Future research should focus on long-term impacts, including smoking-related morbidity and mortality.
Reference:
Hendershot CS, Bremmer MP, Paladino MB, et al. Once-Weekly Semaglutide in Adults With Daily Cigarette Use: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(5):e2614898. doi:10.1001/jamanetworkopen.2026.14898
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