• William Wang, Nora D Volkow, Nathan A Berger, Pamela B Davis, David C Kaelber, and Rong Xu.
• Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio (W.W., N.A.B.).
• Ann. Intern. Med. 2024 Aug 1; 177 (8): 101610271016-1027.

BackgroundReports of reduced desire to smoke in patients treated with semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) medication for type 2 diabetes mellitus (T2DM) and obesity, have raised interest about its potential benefit for tobacco use disorders (TUDs).ObjectiveTo examine the association of semaglutide with TUD-related health care measures in patients with comorbid T2DM and TUD.DesignEmulation target trial based on a nationwide population-based database of patient electronic health records.SettingUnited States, 1 December 2017 to 31 March 2023.ParticipantsSeven target trials were emulated among eligible patients with comorbid T2DM and TUD by comparing the new use of semaglutide versus 7 other antidiabetes medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1RAs).MeasurementsThe TUD-related health care measures (medical encounter for diagnosis of TUD, smoking cessation medication prescriptions, and smoking cessation counseling) that occurred within a 12-month follow-up were examined using Cox proportional hazards and Kaplan-Meier survival analyses.ResultsThe study compared 222 942 new users of antidiabetes medications including 5967 of semaglutide. Semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with other antidiabetes medications, and was strongest compared with insulins (hazard ratio [HR], 0.68 [95% CI, 0.63 to 0.74]) and weakest but statistically significant compared with other GLP-1RAs (HR, 0.88 [CI, 0.81 to 0.96]). Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed in patients with and without a diagnosis of obesity. For most of the group comparisons, the differences occurred within 30 days of prescription initiation.LimitationDocumentation bias, residual confounding, missing data on current smoking behavior, body mass index, and medication adherence.ConclusionSemaglutide was associated with lower risks for TUD-related health care measures in patients with comorbid T2DM and TUD compared with other antidiabetes medications including other GLP-1Ras, primarily within 30 days of prescription. These findings suggest the need for clinical trials to evaluate semaglutide's potential for TUD treatment.Primary Funding SourceNational Institutes of Health.

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