EP416 - ECE_1411 - Risk of incident chronic obstructive pulmonary disease in type 2 diabetes treated with SGLT2 inhibitors or GLP-1 receptor agonists vs DPP-4 inhibitors: a Real-World Cohort Study
Abstract
Patients with type 2 diabetes (T2D) have a higher risk of developing chronic obstructive pulmonary disease (COPD), which is associated with substantial morbidity and mortality. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated pleiotropic cardiometabolic effects and potential pulmonary benefits, their associations with incident COPD risk remain unclear. To evaluate the associations of SGLT2is and GLP-1 RAs, using dipeptidyl peptidase-4 inhibitors (DPP4is) as an active comparator, with the risk of incident COPD in patients with T2D. We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (2015-2024), emulating a target trial with a new-user, active-comparator approach. Adults with T2D initiating SGLT2is or GLP-1 RAs were compared with DPP4i users. Propensity score matching was used to balance baseline demographics, comorbidities, medication use, and laboratory data. Cox proportional hazards models were used to estimate hazard ratios for incident COPD. After propensity score matching, 329,987 matched pairs were included in the SGLT2is vs DPP4is comparison, and 303,020 matched pairs were included in the GLP-1 RAs vs DPP4is comparison. Compared with DPP4is, SGLT2i use was associated with a lower risk of incident COPD (HR, 0.86; 95% CI, 0.84-0.87), and GLP-1 RA use was associated with a similar risk reduction (HR, 0.86; 95% CI, 0.85-0.88). These associations were consistent across age and sex subgroups. In the direct comparison between GLP-1 RAs and SGLT2is (301 664 matched pairs), no significant difference in incident COPD risk was observed (HR, 0.98; 95% CI, 0.96-1.01). SGLT2is and GLP-1 RAs were associated with a significantly lower risk of incident COPD compared with DPP4is in patients with T2D. These findings support the potential respiratory-protective pleiotropic effects of these agents and may inform treatment selection for patients with T2D at risk for chronic lung disease.