B99-08 Glucagon-like Peptide-1 Receptor Agonists and Risk of Tuberculosis in Type 2 Diabetes

Rationale Tuberculosis (TB) remains a major global health challenge and is a leading cause of morbidity and mortality. Patients with type 2 diabetes (T2D) have an elevated risk of TB, yet the influence of different antidiabetic therapies on TB incidence is unclear. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown immunomodulatory properties, but their relationship with TB risk compared with other commonly prescribed antidiabetic medications has not been well defined. Methods We conducted a retrospective cohort study using the TriNetX global federated health research network (January 1, 2017-June 30, 2025), comprising electronic health records from 143 healthcare organizations worldwide. Adults (≥18 years) with T2D (ICD-10-CM E11) initiating GLP-1RAs or comparator therapies (sulfonylureas [SUs], metformin, dipeptidyl peptidase-4 inhibitors [DPP-4is], or sodium-glucose cotransporter-2 inhibitors [SGLT2is]) were included. Patients with prior or concurrent use of study drugs were excluded. Propensity score matching was applied to balance baseline characteristics. Cohort sizes after matching were: GLP-1RA vs SU (n = 613,371 per group), GLP-1RA vs metformin (n = 359,310 per group), GLP-1RA vs DPP-4i (n = 533,713 per group), and GLP-1RA vs SGLT2i (n = 574,060 per group). The primary outcome was TB incidence; secondary outcomes were pulmonary and extrapulmonary TB. Cox proportional hazards models were used to estimate hazard ratios (HRs). Results Among 7,297,342 patients with T2D, GLP-1RA use was consistently associated with a lower TB risk compared with all comparator agents. Incidence rates per 1,000 person-years were significantly reduced in the GLP-1RA group: SU (0.68 vs 1.67; HR, 0.53; 95% CI, 0.47-0.59), metformin (0.65 vs 1.31; HR, 0.60; 95% CI, 0.51-0.70), DPP-4i (0.73 vs 1.71; HR, 0.49; 95% CI, 0.43-0.56), and SGLT2i (0.89 vs 1.02; HR, 0.82; 95% CI, 0.72-0.92). Benefits were consistent across stratified subgroups. Secondary analyses showed significantly reduced risks of pulmonary TB versus all comparators and reduced extrapulmonary TB versus SU and DPP-4i. Conclusions In this large real-world cohort, GLP-1RA initiation was associated with a substantially lower risk of TB compared with multiple standard antidiabetic therapies. These findings suggest that GLP-1RAs may provide protective effects beyond glycemic control, with important implications for treatment selection in regions with high TB burden. This abstract is funded by: None