Once-weekly Semaglutide significantly reduced laboratory smoking resistance in daily cigarette users

Cigarette smoking is a leading cause of preventable morbidity and mortality, significantly increasing the risk of cardiometabolic diseases. Current smoking cessation strategies often have limited efficacy, and many individuals struggle with relapse. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, have shown promise in preclinical and early clinical studies for their potential to influence reward pathways and reduce addictive behaviors, alongside their established benefits in weight management and cardiovascular risk reduction. This study explores GLP-1RA's potential to address the dual challenge of smoking cessation and associated cardiometabolic risks.

This phase 2a randomized clinical trial enrolled 45 non-treatment-seeking adults who smoked at least 5 cigarettes per day. 24 participants were randomized to receive either once-weekly subcutaneous semaglutide or placebo for 9 weeks. The semaglutide dosing regimen was 0.25 mg for 4 weeks, followed by 0.5 mg for 4 weeks, and finally 1.0 mg for 1 week. Co-primary outcomes included laboratory measures of smoking resistance, reinstatement, and self-administration, assessed before and after treatment. Weekly assessments tracked changes in cigarette use, craving, and body weight.

Of the 24 randomized participants, 21 (88%) completed the primary outcome assessment. Primary treatment-by-time interactions for laboratory measures of smoking resistance (β = 0.16 [95% CI, -0.07 to 0.40]; P = .16) and number of cigarettes (β = -0.08 [95% CI, -0.25 to 0.08]; P = .30) were not statistically significant. However, supplementary change score analyses revealed a significant reduction in laboratory smoking in the semaglutide group.

Semaglutide treatment led to significantly greater reductions in laboratory smoking (β = -0.69 [95% CI, -1.26 to -0.13]; P = .02; d = 0.67) compared to placebo. This indicates an effect on smoking behavior, despite the primary outcomes not reaching statistical significance. The study also assessed changes in cigarette use, craving, and body weight weekly, though specific numbers for these secondary outcomes were not detailed in the abstract.