Semaglutide misses smoking-resistance endpoint but cuts craving in small trial

Once-weekly semaglutide did not significantly improve a laboratory measure of smoking resistance in adults who smoke daily, according to an eight-week randomized clinical trial published in JAMA Network Open ^[1]. The trial did report significant reductions in weekly cigarette craving, body weight and hemoglobin A1c ^[1].

The study, "Once-Weekly Semaglutide in Adults With Daily Cigarette Use: A Randomized Clinical Trial," appears in the journal's substance use and addiction section ^[1]. Participants were assessed in laboratory sessions after treatment week 8, when the semaglutide dose was 0.5 mg per week ^[1]. The trial compared medication conditions and doses, and reported adverse events by medication condition and dose in a supplementary table ^[1].

The main laboratory test had two parts: how long participants delayed before smoking, measured in minutes, and how many cigarettes they smoked ^[1]. The results figures show 19 participants for the delay-time measure and 16 for the cigarette-count measure ^[1]. The trial's participant enrollment flowchart appears in the paper ^[1]. The full enrollment total and the breakdown of dropouts are not reported in the article's summary text ^[1].

Beyond the laboratory test, the trial tracked weekly cigarettes per day and craving, weight and clinical outcomes including HbA1c, withdrawal symptoms on the Wisconsin Smoking Withdrawal Scale, and how participants rated the first cigarette they smoked after treatment ^[1]. Craving, weight and HbA1c are presented as line graphs by study week, with the underlying statistical models reported in supplementary tables ^[1]. The numeric size of those changes is not stated in the article's results text ^[1].

Semaglutide is sold as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for chronic weight management, and smoking cessation is not an approved use of any of them. The weight and blood-sugar improvements seen in this trial line up with what the drug is already prescribed to do ^[1].

Why it matters for patients

A drop in craving is not the same as quitting. The trial's main laboratory endpoint was not met, so this study does not show that semaglutide helps people stop smoking ^[1]. Craving was one of several secondary outcomes, and a signal in a secondary measure from a small, short study is weaker evidence than a result on the primary endpoint.

The trial was small and lasted eight weeks ^[1]. Whether semaglutide changes smoking behavior over months, or whether it helps anyone quit for good, has not been reported by this trial ^[1]. Weight loss and lower HbA1c are expected effects of semaglutide, so finding them here does not by itself show the drug is acting on nicotine dependence.

For people already taking Ozempic, Wegovy or Rybelsus for diabetes or weight management, this trial does not change what is known about those uses ^[1]. Nothing in the results indicates the drug should be started or stopped for smoking. Safety findings by dose appear in the trial's supplementary table, and rates are not given in the article's summary sections ^[1].

The trial does not say how semaglutide compares with other ways of quitting smoking, because it tested semaglutide itself rather than a head-to-head comparison ^[1].

What happens next

The paper does not describe a larger follow-up trial, a regulatory filing, or any plan to seek a smoking-cessation indication for semaglutide ^[1]. No date for further results in this line of research has been announced ^[1]. Until larger trials report, the question of whether semaglutide can help people quit smoking remains open.