Antihyperglycemic Drugs and Risk of Asthma Exacerbation in Patients With Asthma and Type 2 Diabetes: A Multinational Retrospective Cohort Study

BACKGROUND: Antihyperglycemic drugs have shown benefits in asthma control. However, evidence regarding the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) in reducing asthma exacerbations remains inconsistent. OBJECTIVE: We aimed to evaluate the association of GLP-1 RAs versus SGLT-2is with risk of asthma exacerbation among patients with asthma and type 2 diabetes. METHODS: This retrospective cohort study used electronic health record data from the TriNetX Global Collaborative Network. Adults with asthma and type 2 diabetes who initiated GLP-1 RAs or SGLT-2is between January 1, 2013, and June 30, 2024, were included. The primary outcome was the time to first asthma exacerbation. Secondary outcomes included first episode of asthma symptoms or systemic corticosteroid use. Patients were followed for up to 6 months in the main analysis. Propensity score matching was performed to balance baseline characteristics between groups. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 100,746 patients were included, comprising 61,955 GLP-1 RA users and 38,791 SGLT-2i users. After 1:1 matching, both groups consisted of 28,831 patients. GLP-1 RAs were associated with a decreased risk of asthma exacerbation compared with SGLT-2is (HR, 0.88; 95% CI, 0.85-0.91). GLP-1 RAs were also associated with a decreased risk of experiencing asthma symptoms (HR, 0.89; 95% CI, 0.82-0.97) and receiving systemic corticosteroids (HR, 0.79; 95% CI, 0.76-0.82). Results from sensitivity analyses were generally consistent, but the association for asthma exacerbation was not observed when follow-up was extended to 1 year (HR, 0.95; 95% CI, 0.89-1.02). CONCLUSION: GLP-1 RAs were associated with a decreased risk of asthma exacerbation compared to SGLT-2is among patients with asthma and type 2 diabetes. As these findings reflect associations rather than causal effects, further investigation through randomized trials is warranted.