Comparative Effects of Tirzepatide and Semaglutide on Asthma-Related Complications: A Target Trial Emulation Using the TriNetX Networks

Abstract Objective Tirzepatide and semaglutide are widely administered for individuals with type 2 diabetes mellitus (T2DM) or obesity. In this study, we aimed to evaluate the overall impact of these medications on patients with asthma. Patients and Methods This retrospective cohort was based on data from the TriNetX US Collaborative Network for patients who received either tirzepatide or semaglutide between June 1, 2022, and December 1, 2023. After propensity score matching on baseline profile, 2,239 patients were indentifed in both cohorts. The follow-up started from Day 1 after drug initiation, and continued up to Day 365. Results Compared to the semaglutide cohort, the tirzepatide cohort had higher risks of obstructive sleep apnea (OSA) (HR = 1.122; 95% CI: 1.015–1.239; p = 0.024) and sleep apnea (HR = 1.115; 95% CI: 1.014–1.226; p = 0.024). Subgroup analysis on patients with T2DM found that the risk for OSA (HR = 1.252; 95% CI: 1.021–1.534; p = 0.030) and sleep apnea (HR = 1.273; 95% CI: 1.050–1.544; p = 0.014) were also elevated. For patients without T2DM, the use of tirzepatide was related to a lower risk of receiving antiasthmatic bronchodilators (HR = 0.860; 95% CI: 0.745–0.993; p= 0.040). Conclusion Tirzepatide use in asthma patients, particularly those with coexisting T2DM, may be associated with a higher risk of OSA compared to semaglutide. In asthma patients without T2DM, tirzepatide may reduce the need for bronchodilators.