Sepsis risk in patients with COPD and type 2 diabetes mellitus: influence of emerging antihyperglycemic therapies

BACKGROUND AND OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are at increased risk of sepsis, yet the comparative infection-related outcomes of newer antihyperglycemic agents remain unclear. We evaluated the associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus sodium-glucose cotransporter 2 inhibitors (SGLT2is) with infection outcomes in this population. METHODS: In this retrospective cohort study using the TriNetX global federated database, individuals aged 40-100 years with coexisting COPD and T2DM who initiated a GLP-1RA or SGLT2i between 2021 and 2024 were identified. A new-user, active-comparator design with 1:1 propensity score matching was applied. Sepsis was the primary outcome; all-cause mortality and components of the primary outcome were secondary. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: After matching, 45,491 pairs were included. Compared with SGLT2is, GLP-1RAs showed lower risks of sepsis (adjusted HR, 0.832; 95% CI, 0.781-0.887), all-cause mortality (0.642; 0.598-0.689), and severe sepsis (0.841; 0.774-0.914). CONCLUSION: In patients with COPD and T2DM, GLP-1RAs were associated with significantly lower risks of sepsis and all-cause mortality compared with SGLT2is.