(101) Use of SGLT2 inhibitors vs. GLP-1 RAs and Asthma Exacerbation in Patients with Diabetes and Asthma – A target Trial Emulation Study

Background: Better glycemic controls in patients with diabetes may be associated with a lower incidence of subsequent asthma exacerbation. Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors and Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been proven with the similar glucose-lowering effects in the real-world practice; theoretically, the comparison of asthma exacerbation risk between these two drug classes would be similar.

Objectives: To evaluate the use of SGLT2 inhibitors vs GLP-1 RAs and asthma exacerbation in patients with diabetes and asthma in the routine care practice.

Methods: We conducted a retrospective cohort study analyzing the National Health Insurance Research Database (NHIRD). Our study included adult patients with type 2 diabetes and asthma without the history of asthma exacerbation newly prescribed with either SGLT-2 inhibitors or GLP-1 RAs between 2016 and 2020. We applied target trial emulation framework to enhance the causal inferences, and used propensity score matching to mimic the randomization process between SGLT2 inhibitor or GLP-1 RA new users. Composite asthma exacerbation outcome was defined as (1) either clinical visits with the diagnosis of asthma exacerbation, or (2) systemic corticosteroid use. Eligible patients would be followed from the initiations of SGLT2 inhibitors or GLP-1 RAs to the outcome occurrence, death, or the end of database (December 31, 2020). To determine the internal study validity, we also compared the all-cause death risk between SGLT2 inhibitor or GLP-1 RA new users which were assumed with no differences between these two drug classes. The hazard ratios (HR) and 95% confidence interval (95% CI) were estimated by the Cox proportional hazards model.

Results: We included a total of 11,206 patients with 10,268 receiving SGLT2 inhibitors (mean age: 61.8 years, SD: 13.3; male: 49.5%) and 938 receiving GLP-1 RAs (mean age: 61.4 years, SD: 13.8; male: 50.5%). After the mean follow-up of 2.2 years, we found the similar risk of composite asthma exacerbation outcome between SGLT2 inhibitors and GLP-1 RAs (HR, 0.97; 95% CI, 0.74-1.30). Results from individual outcomes were consistent to the primary analysis, including clinical visits (HR, 0.98; 95% CI, 0.75-1.30), and systemic corticosteroid use (HR, 1.13; 95% CI, 0.59-2.17). The similar all-cause mortality risk between SGLT2 inhibitors and GLP-1 RAs (HR, 0.88; 95% CI, 0.64-1.20) reassured the study internal validity.

Conclusions: Our finding suggested no significant risk difference of subsequent asthma exacerbation between SGLT2 inhibitors and GLP-1 RAs in the routine care practice in Taiwan. The choice of these two novel anti-diabetes medications for type 2 diabetes with asthma should be based on other clinical considerations and large-scaled evidence.