Association of Glucagon-like Peptide-1 Receptor Agonists Versus Dipeptidyl Peptidase-4 Inhibitors with Tuberculosis and Mortality in Adults with Diabetes

Diabetes is associated with an increased risk of tuberculosis (TB), but whether the class of glucose-lowering therapy is associated with TB outcomes remains uncertain. We conducted a retrospective observational cohort study to examine the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use versus dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of TB and mortality. We used de-identified records from the TriNetX Global Collaborative Network. Adults with diabetes who had a qualifying record for either a GLP-1 RA or a DPP-4i between 2016 and 2024 were eligible. Cohort entry was defined as the first qualifying drug-class record during this period. Patients with prior-year use of the comparator drug class, a history of TB, or death before cohort entry were excluded. Propensity score matching was performed at a 1:1 ratio. Outcomes assessed during days 1–365 included TB (ICD-10-CM A15–A19), the platform-defined death outcome, and a composite outcome of gastrointestinal and hepatobiliary diagnoses. After matching, 466,903 patients remained in each group. GLP-1 RA exposure was associated with fewer recorded TB events, deaths, and gastrointestinal/hepatobiliary events than DPP-4i exposure during the first year after cohort entry. TB was recorded in 155 GLP-1 RA users and 320 DPP-4i users (HR, 0.472; 95% CI, 0.390–0.572). The corresponding numbers for the platform-defined death outcome were 7575 and 14,572 (HR, 0.505; 95% CI, 0.492–0.520), and those for gastrointestinal/hepatobiliary diagnoses were 15,914 and 20,559 (HR, 0.750; 95% CI, 0.735–0.766). The analysis restricted to patients with type 2 diabetes (ICD-10-CM E11) yielded a similar association for TB. Residual imbalance in body mass index (BMI) and residual confounding, including confounding by indication, limit a causal interpretation.