Association between GLP-1 receptor agonist use and risk of pneumonia and pyothorax in type 2 diabetes: a retrospective cohort study

To assess the association between Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and the incidence of pneumonia and pyothorax in patients with Type 2 diabetes mellitus (T2DM). T2DM is associated with an increased risk of pneumonia and its complications, including pyothorax. GLP-1 RAs, a class of antidiabetic medications, have demonstrated anti-inflammatory and cardiometabolic benefits, but their influence on infectious complications remains underexplored. This retrospective cohort study was conducted using data from the TriNetX U.S. collaborative network, which comprises electronic health records of over 116 million patients. Adults aged ≥ 20 years with a new diagnosis of type 2 diabetes mellitus (T2DM) between 2016 and 2023 were identified. Patients were divided into two groups based on exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus non–GLP-1 RA treatments. After applying exclusion criteria and performing 1:1 propensity score matching for demographics, comorbidities, medications, and relevant laboratory values, a total of 181,634 patients were included in the matched cohorts. The primary outcome was the incidence of pneumonia (ICD-10-CM codes J12–J18) and pyothorax (ICD-10-CM code J86). The incidence of pneumonia and pyothorax was significantly lower in the GLP-1 RA group (15.20%) compared to the non–GLP-1 RA group (18.54%), with a hazard ratio (HR) of 0.76 (95% CI: 0.74–0.78). GLP-1 RA use was also associated with reduced risk of pyothorax (HR = 0.58, 95% CI: 0.46–0.73). These protective effects were consistent across subgroups stratified by age, sex, race, and BMI, although not statistically significant among Asian and African American populations, likely due to limited sample size. GLP-1 RA therapy in T2DM patients is associated with a significantly lower risk of pneumonia and pyothorax, potentially mediated through anti-inflammatory and metabolic benefits. These findings support the broader role of GLP-1 RAs in mitigating infection-related complications in diabetes care. Not applicable. GLP-1 receptor agonists were associated with a 24% reduction in pneumonia risk (HR = 0.76). GLP-1 RAs led to a 42% reduction in the risk of pyothorax (HR = 0.58). Protective effects were consistent across age, sex, BMI, and racial subgroups, though not statistically significant in Asian and African American groups. This is the first large-scale cohort study to assess GLP-1 RA impact on pyothorax in T2DM patients. The findings suggest potential anti-inflammatory and immunomodulatory roles of GLP-1 RAs beyond glycemic control.