Pulmonary outcomes of incretin-based therapies in COPD patients receiving single-inhaler triple therapy.

Background: Patients with COPD on triple therapy often face exacerbations and comorbidities. Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) analogues may reduce the risk of exacerbation in patients with COPD and type 2 diabetes mellitus (T2DM). This study investigates the impact of GLP-1 analogues on pulmonary outcomes in patients with COPD on single-inhaler triple therapy (SITT) and T2DM. Methods: We conducted a retrospective cohort study using the TriNetX database and analysed adult patients with COPD and T2DM who received SITT between April 2005 and July 2023. Patients were categorised into GLP-1 analogue and dipeptidyl peptidase-4 inhibitor (DPP4i) cohorts. The primary efficacy outcome was COPD exacerbation, and the secondary efficacy outcomes were pneumonia, acute respiratory distress syndrome, intubation, oxygen dependence and all-cause mortality. The secondary outcomes were serious gastrointestinal adverse events. Results: We included 6898 patients, with 4184 receiving GLP-1 analogues and 2714 receiving DPP4i. After matching, 1751 GLP-1 analogue users were matched with 1751 DPP4i users. GLP-1 analogue users had an 18% lower risk of COPD exacerbation (hazard ratio (HR) 0.82 (95% CI 0.71-0.94)), a 28% reduced risk of pneumonia (HR 0.72 (95% CI 0.61-0.85)), a 34% reduced risk of oxygen dependence (HR 0.66 (95% CI 0.47-0.91)) and a 40% decreased risk of all-cause mortality (HR 0.60 (95% CI 0.47-0.77)). No significant serious gastrointestinal adverse events were observed. Conclusion: GLP-1 analogues may be associated with reduced COPD exacerbations, pulmonary comorbidities and mortality in patients with COPD receiving SITT and T2DM, with no significant serious gastrointestinal safety concerns.