Association of Glucagon-like Peptide-1 Receptor Agonists with Mortality and Aspiration Pneumonia in Patients with Type 2 Diabetes After Gastrostomy: A Target Trial Emulation Study

Background: This study aimed to compare the safety and effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes following gastrostomy.Methods: We conducted a target trial emulation using real-world data.From January 1, 2015, to December 31, 2024, we identified 728 patients who initiated either GLP-1 RA or DPP-4i after gastrostomy.After 1:1 propensity score matching to balance baseline covariates, 364 patients were included in each group.The primary analysis followed an intention-to-treat principle, and follow-up continued until June 30, 2025.Several sensitivity analyses, including landmark analysis and E-value calculation, were performed to assess the robustness of the findings.Results: Compared with DPP-4i initiation, GLP-1 RA initiation was associated with lower all-cause mortality (adjusted hazard ratio [aHR], 0.71; 95% confidence interval [CI], 0.54-0.93)and aspiration pneumonia (aHR, 0.64; 95% CI, 0.44-0.93).Conclusions: Our findings indicate that initiation of GLP-1 RA, compared with initiation of DPP-4i, was associated with lower all-cause mortality and a lower risk of aspiration pneumonia in patients with type 2 diabetes following gastrostomy.Further prospective studies are warranted to confirm these findings in this vulnerable population.