Abstract Body: Background
There is evidence that several treatments for type 2 diabetes may reduce asthma exacerbations, but prior studies had small sample sizes and short follow-ups. The objective is to assess the impact of glucagon-like peptide-1 receptor agonists (GLP-1Ra) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) on asthma exacerbations among adults with type 2 diabetes and asthma.

Methods
We used TriNetX electronic medical records from 79 U.S. healthcare organizations from January 2015 to November 2023. We emulated a trial comparing GLP-1Ra’s to DPP-4i’s and another comparing GLP-1Ra’s to SGLT-2i’s, 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 without other recently prescribed second-line antidiabetic medications. We followed individuals until their first asthma exacerbation, death, or the end of 12 months of follow-up, and we 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, asthma severity, and initiation year.

Results
The study included 10,173 new users on GLP-1Ra’s (n=4,499), DPP-4i’s (n=3,169), and SGLT-2i’s (n=2,478). The 12-month risk ratio (RR) for asthma exacerbations was 0.93 (95% confidence intervals [CI], 0.83–1.05) for GLP-1Ra versus DPP-4i, suggesting a nominally lower exacerbation risk. No statistically significant difference in the likelihood of asthma exacerbations was observed between GLP-1Ra and SGLT-2i (RR 1.04, 95% CI 0.92–1.15). Differences between GLP-1Ra’s and DPP-4i’s were largely driven by fewer asthma-related hospitalizations with GLP-1Ra’s (RR 0.76, 95% CI 0.59–0.98). Sensitivity and subgroup analyses were consistent, with lower risks among individuals with obesity and those initiating therapy in more recent years.

Conclusions
In this large, diverse U.S. cohort, GLP-1Ra initiation was not associated with significant differences in 12-month asthma exacerbation risks compared with SGLT-2i’s or DPP-4i’s, although exploratory analyses suggested fewer hospitalizations compared with DPP-4i’s and potential benefit among individuals with obesity.