A Comparison of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors in Reducing the Incidence of Tuberculosis and Mortality in Patients with Diabetes

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Abstract

Diabetes mellitus (DM) significantly increases the risk of developing active tuberculosis (TB). Poorly controlled diabetes, particularly with sustained hyperglycemia, is associated with higher TB incidence. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become an important therapeutic option in the management of type 2 diabetes mellitus. GLP-1 RAs may also have immunomodulatory effects. Our study aims to evaluate the incidence of pulmonary TB among diabetic patients, and to examine whether GLP-1 RAs control modifies TB risk and mortality. We conducted a retrospective cohort study using the Global Collaborative Network of the TriNetX™ research platform from 152 participating health care organizations across the United States. We identified adult patients with diabetes mellitus who received either oral hypoglycemic agents (OHAs) containing GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) between January 1, 2016, and December 31, 2024. Diabetic patients receiving OHAs containing GLP-1 RA treatment had a significantly lower incidence of TB (HR: 0.55, 95% CI: 0.45-0.69), significantly reduced risk of death (HR: 0.52, 95% CI: 0.51-0.54), and significantly reduced risk of gastrointestinal and hepatobiliary disorders (HR: 0.77, 95% CI: 0.75-0.78), compared to those receiving DPP-4 inhibitor treatment. This observational study demonstrated that the use of GLP-1 RAs, compared with DPP-4i, was associated with a lower incidence of tuberculosis, all-cause mortality, and gastrointestinal adverse events. These findings may have important implications for public health policy.

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