(A-125) Impact of GLP-1 Receptor Agonists versus DPP-4 Inhibitors and SGLT-2 Inhibitors on Asthma Exacerbations Among Individuals with Asthma and Type 2 Diabetes: A Target Trial Emulation Study

Background: Existing evidence suggests that several treatments for type 2 diabetes may reduce asthma exacerbations among individuals with type 2 diabetes and asthma. However, prior studies have had small sample sizes and short follow-ups.

Objectives: To assess the impact of glucagon-like peptide-1 receptor agonist (GLP-1Ra) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) on asthma exacerbation risks among adults with both asthma and type 2 diabetes.

Methods: We conducted a retrospective cohort study using electronic medical records data from 79 U.S. healthcare organizations in the TriNetX database from January 2015 to November 2023. We emulated a trial comparing GLP-1Ra to DPP-4i and another comparing GLP-1Ra to SGLT-2i, focusing on the impact on asthma exacerbations for adults diagnosed with asthma and type 2 diabetes. The study population included adults aged 18 years or older with both type 2 diabetes and asthma, not recently prescribed other second-line antidiabetic medications. We followed individuals until the first asthma exacerbation, death, or end of one year follow-up, and pre-defined asthma exacerbation as a composite of asthma-related hospitalizations, emergency room visits, or new systemic corticosteroid use. We used stabilized inverse probability weights to balance baseline covariates and pooled logistic regression to estimate risk ratios with bootstrapping for confidence intervals. Subgroups included obesity, sex, recent metformin use, and asthma severity. Additionally, we used zero-inflated Poisson regression models to compare one-year asthma exacerbation counts.

Results: The study included 10,273 new users on GLP-1Ra (n=4,542), SGLT-2i (n=2,499), and DPP-4i (n=3,232). The risk ratio (RR) at week 52 for asthma exacerbations was 0.93 (95% confidence interval [CI], 0.83–1.03) for GLP-1Ra versus DPP-4i, suggesting a nominally lower exacerbation risk with GLP-1Ra, although the association was not statistically significant. No statistically significant difference in the likelihood of asthma exacerbation was observed among GLP-1Ra and SGLT-2i recipients (RR: 1.04, 95% CI: 0.92–1.15). Subgroup analyses suggested nominally lower, though not statistically significant, asthma exacerbation risks with GLP-1Ra among males (RR: 0.85, 95% CI: 0.66–1.08) and those with recent metformin use (RR: 0.93, 95% CI: 0.79–1.09). No statistically significant differences were found in the one-year asthma exacerbation counts in either comparison.

Conclusions: Among this large, diverse cohort of U.S. adults with asthma and type 2 diabetes, asthma exacerbation risks over one year were generally comparable across GLP-1Ra, SGLT-2i, and DPP-4i.