Target trial emulation of DPP-4 Inhibitors in patients with T2DM for pulmonary tuberculosis

Background: Diabetes mellitus increases the risk of developing tuberculosis (TB) and negatively affects TB treatment outcomes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in glycemic control but can also modulate immune pathways involved in immune-mediated diseases. Considering the immunoregulatory effects of DPP-4 inhibitors, this emulated target trial compared the risk of pulmonary TB in users and non-users of DPP-4 inhibitors with type 2 diabetes mellitus (T2DM). Methods: We identified 328,842 pairs of DPP-4 inhibitor users and non-users from Taiwan’s National Health Insurance Research Database from January 1, 2007, and December 31, 2019. Cox proportional hazard models were used to determine the risk of new-onset pulmonary TB between the study and control groups. Results: The follow-up duration was 5.06 years for DPP-4 inhibitor users and 4.05 years for non-users. The incidence rates of new-onset pulmonary TB were 1.93 and 2.18 cases per 1,000 person-years in DPP-4 inhibitor users and non-users, respectively. Compared with non-users, DPP-4 inhibitor users had a significantly lower risk of developing pulmonary TB, with an adjusted hazard ratio (aHR) of 0.85 (95% CI: 0.81–0.90). Kaplan–Meier analysis showed a significantly lower cumulative incidence of new-onset pulmonary TB among DPP-4 inhibitor users than non-users (log-rank test, p < 0.001). Furthermore, a longer cumulative duration of DPP-4 inhibitor use was associated with a lower risk of pulmonary TB. Conclusions: In patients with T2DM, the use of DPP-4 inhibitors was associated with a significantly lower risk of developing pulmonary TB compared to non-use. Additionally, a longer cumulative duration of DPP-4 inhibitor may further reduce the TB risk.