Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes: Target Trial Emulation Using Real-World Data
Open accessAbstract
BACKGROUND: Reports 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). OBJECTIVE: To examine the association of semaglutide with TUD-related health care measures in patients with comorbid T2DM and TUD. DESIGN: Emulation target trial based on a nationwide population-based database of patient electronic health records. SETTING: United States, 1 December 2017 to 31 March 2023. PARTICIPANTS: Seven 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). MEASUREMENTS: The 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. RESULTS: The 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. LIMITATION: Documentation bias, residual confounding, missing data on current smoking behavior, body mass index, and medication adherence. CONCLUSION: Semaglutide 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 SOURCE: National Institutes of Health.
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Semaglutide use is associated with a lower risk of tobacco use disorder-related healthcare encounters, including diagnosis (HR 0.68), prescriptions for cessation medications (HR 0.32), and cessation counseling (HR 0.72) compared to insulin.
“In contrast, real-world data from a target trial emulation found that semaglutide use was associated with a lower risk of tobacco use disorder-related healthcare encounters, including diagnosis (HR vs. insulin: 0.68, 95% CI 0.63, 0.74), prescriptions for cessation medications (HR: 0.32, 95% CI 0.28, 0.38), and cessation counseling (HR: 0.72, 95% CI 0.58, 0.90).60”
From The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions (2025) · cites this paper as [60]
The Results sections for TUD diagnosis and cessation-medication prescriptions report the insulin comparisons exactly: HR 0.68 (95% CI 0.63–0.74) and HR 0.32 (95% CI 0.28–0.38). The counseling Results section reports a significantly lower risk versus insulin, but our copy does not give the claimed counseling HR of 0.72 or its confidence interval. (LLM, conf=0.86)
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- Authors
- Wang, W., Volkow, N. D., Berger, N. A., Davis, P. B., Kaelber, D. C., & Xu, R.
- Affiliations
- Case Western Reserve University (US)
- National Institutes of Health (US)
- MetroHealth (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2024-08
- Volume
- 177
- Issue
- 8
- Pages
- 1016-1027
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC12721465
- OpenAlex
- W4401068727
- Cited by
- 72
- References
- 42
- Citations by year
- 2026: 35 · 2025: 27 · 2024: 10
- FWCI
- 20.36
- Type
- journal article
- Language
- en
- Open access
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UM1TR004528)
- National Institute on Alcohol Abuse and Alcoholism (R01AA029831)
- National Institute on Aging (R01AG061388, R56AG062272, RF1AG076649, R01AG057557, R01AG076649)
- National Cancer Institute (P30CA043703, R25CA221718)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- semaglutide, tobacco use disorder, type 2 diabetes, smoking cessation, GLP-1 receptor agonists, smoking cessation counseling, obesity, health care utilization, electronic health records, insulin, SGLT2 inhibitors, DPP-4 inhibitors, thiazolidinediones, sulfonylureas, metformin
- MeSH terms
- Semaglutide, Aged, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Obesity, Tobacco Use Disorder, United States, Smoking Cessation
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