SGLT2 Inhibitors and Asthma Exacerbation Risk Among Patients With Type 2 Diabetes and Asthma: A Target Trial Emulation.

Emerging evidence suggests potential respiratory benefits from sodium-glucose cotransporter 2 (SGLT2) inhibitors, a glucose-lowering agent. However, the effects of these agents on asthma exacerbations remain unclear. A retrospective cohort study used Taiwan's National Health Insurance Research Database, covering 2016-2020, and included adults with type 2 diabetes and asthma. Exposure was defined as the initiation of SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors, and the primary outcome was asthma exacerbation, defined as an asthma diagnosis accompanied by systemic corticosteroid use. Demographic characteristics, comorbidities, the Adapted Diabetes Complications Severity Index and concomitant medications were used to estimate propensity scores, and inverse probability of treatment weighting was applied. Altogether, 3,057 initiators of SGLT2 inhibitors and 15,050 initiators of DPP4 inhibitors were identified and followed from the index date until the occurrence of asthma exacerbation, death, or the end of the observation period (May 31, 2020). Over a mean follow-up of 2.06 years, initiation of SGLT2 inhibitors was associated with a lower risk of asthma exacerbation (HR: 0.87, 95% CI: 0.81-0.93), corresponding to incidence rates of 3.73 vs. 4.03 events per 100 person-years. The results were consistent across care settings, including outpatient- (HR: 0.88, 95% CI: 0.80-0.96), inpatient- (HR: 0.88, 95% CI: 0.78-1.00), and emergency department visits (HR: 0.72, 95% CI: 0.63-0.83), as also across subgroup and sensitivity analyses. Among adults with type 2 diabetes and asthma, initiation of SGLT2 inhibitors was associated with a reduced risk of asthma exacerbation, highlighting a potential respiratory benefit that warrants confirmation through future clinical trials.