Research Square · Oct 20, 2026

Pulmonary Aspiration and Related Outcomes Associated with Semaglutide and Tirzepatide: A Comparative Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

By Sarıca O

Background Incretin-based therapies, including the GLP-1 receptor agonist semaglutide and the dual GIP/GLP-1 receptor co-agonist tirzepatide, delay gastric emptying, raising clinical concerns regarding pulmonary aspiration. This study evaluates serious clinical outcomes among pulmonary aspiration-related adverse event reports and characterizes dual-exposure cases. Methods Adverse event reports associated with pulmonary aspiration and aspiration pneumonia were identified from the FDA Adverse Event Reporting System (FAERS). Reports listing both agents as suspect products were segregated into an independent co-reported cohort (n = 7). Single-agent semaglutide (n = 132) and tirzepatide (n = 79) cohorts were analyzed for demographic profiles and serious clinical outcomes (death, hospitalization, and life-threatening events). Fisher's exact tests were performed to compare outcomes between cohorts. Results A total of 218 cases were analyzed. In the semaglutide cohort (n = 132; mean age 61.1, SD (standard deviation) 14.6 years; 48.5% female), mortality was 17.4% and hospitalization was 62.1%. In the tirzepatide cohort (n = 79; mean age 65.2, SD 15.4 years; 51.9% female), mortality was 16.5% and hospitalization was 53.2%. Mortality (p = 1.000, OR = 1.071) and hospitalization (p = 0.2477, OR = 1.445) showed no significant differences between groups. However, reports designated as life-threatening were significantly more frequent with tirzepatide compared to semaglutide (17.7% vs. 7.6%; p = 0.0417, OR = 0.381). In the co-reported cohort (n = 7), 57.1% required hospitalization, with no deaths or life-threatening events reported. Conclusion Spontaneous reports of pulmonary aspiration associated with semaglutide and tirzepatide demonstrate similar frequencies of mortality and hospitalization, but a higher proportion of life-threatening designations in tirzepatide cases. Identifying and isolating co-reported cases prevents cross-contamination in incretin pharmacovigilance studies.

doi.org/10.21203/rs.3.rs-11391047/v1 Open access Interventions