Association of Tirzepatide versus Semaglutide with Risk of Asthma Exacerbation in Patients with Asthma and Type 2 Diabetes: A US Multicenter Retrospective Cohort Study.

BACKGROUND: While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise in improving respiratory outcomes, the comparative effectiveness of dual glucose-dependent insulinotropic polypeptide/GLP-1 RA versus GLP-1 RA alone remains unclear. OBJECTIVE: To assess the association of tirzepatide versus semaglutide with the risk of asthma exacerbation among patients with asthma and type 2 diabetes (T2D). METHODS: Data from the TriNetX US Collaborative Network were used. Adults with asthma and T2D who initiated tirzepatide or semaglutide between June 01, 2022, and December 31, 2024, were included. The study period ended on December 1, 2025. The primary outcome was time to first asthma exacerbation over a 12-month follow-up. Secondary outcomes included systemic corticosteroid and short-acting beta-agonist (SABA) use. Propensity score matching was used to balance baseline covariates. Kaplan-Meier curves and Cox regression models were used to estimate comparative effectiveness. RESULTS: After 1:1 matching, 8176 patients were included in each group. The risk of asthma exacerbation was similar between tirzepatide and semaglutide (11.0% vs 11.1%; HR, 1.00; 95% CI, 0.91-1.10). This finding remained consistent across sensitivity and subgroup analyses. For secondary outcomes, tirzepatide was associated with a lower risk of SABA use (HR, 0.92; 95% CI, 0.88-0.96) and a similar risk of systemic corticosteroid use (HR, 1.01; 95% CI, 0.96-1.05) compared with semaglutide. CONCLUSION: Among patients with asthma and T2D, no difference in the risk of asthma exacerbation between tirzepatide and semaglutide was observed. Further investigation through randomized controlled trials is warranted to clarify the potential role of GLP-1 RA-based therapies in patients with asthma and T2D.