Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes: Target Trial Emulation Using Real-World Data
Abstract
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.