PMID-39074369 — Wang: Semaglutide + Tobacco Use Disorder (Target Trial Emulation, Ann Intern Med 2024)

[DRAFT — authored 2026-04-20. Citation verified against PubMed and Annals of Internal Medicine 2026-04-20.]

Citation

Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes: Target Trial Emulation Using Real-World Data. Ann Intern Med. 2024;177(8):1016-1027. doi: 10.7326/M23-2718. PMID: 39074369.

External URL: PubMed

Study Design

Design: Target trial emulation using real-world electronic health record data
Data source: Nationwide US EHR database
Study period: December 1, 2017 – March 31, 2023
Comparators: New use of semaglutide vs seven other antidiabetes medications (including other GLP-1 RAs — liraglutide, dulaglutide, exenatide — plus insulin, DPP-4i, SGLT2i, sulfonylurea, metformin)
Population: Adults with type 2 diabetes + comorbid tobacco use disorder (TUD)
Outcome measures: TUD-related health care measures — medical encounters, smoking-cessation medication prescriptions, nicotine-replacement therapy use, incident TUD diagnoses

Key Findings

Semaglutide was associated with lower risks for TUD-related health care measures in patients with comorbid T2D + TUD compared with other antidiabetes medications — including other GLP-1 RAs.
Effects primarily within 30 days of prescription — suggests an acute pharmacological effect on tobacco craving/use rather than cumulative behavioral change.
Applied target trial emulation methodology — stronger causal inference than naïve observational comparisons, though inherent EHR limitations remain.

Clinical Relevance

Wang 2024 provides real-world observational evidence consistent with a hypothesized role of GLP-1 RAs in modulating reward-regulation disorders. Core teaching points:

Hypothesis-generating, not confirmatory. Target trial emulation reduces confounding but does not approach the rigor of an RCT. The observed signal motivates confirmatory Phase 3 trials.
Companion to Hendershot Phase 2 AUD RCT (PMID 39937469) — both suggest a class-level effect on addictive/reward-regulation behavior.
Dedicated smoking-cessation protocols ongoing — see PMID 40554081 (Yammine Phase 2 protocol, n=177 smokers with overweight/obesity).
Real-world prescribing implication: In T2D patients with comorbid tobacco use, semaglutide's association with reduced TUD-related care measures is a reasonable consideration in shared decision-making — but tobacco cessation remains an off-label benefit, not an approved indication.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (Emerging Indications)

Related Studies

PMID-39937469 – Hendershot Semaglutide Alcohol Use Disorder RCT — AUD Phase 2 companion
PMID-40554081 – Yammine Semaglutide Smoking Cessation Protocol — Phase 2 smoking-cessation trial protocol
PMID-41126551 – Psychiatric Effects GLP1 Systematic Review — broader psychiatric-effects SR

PMID-39074369 – Wang Semaglutide Tobacco Use Disorder Ann Intern Med