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

Yi-Geng Chen1, James Cheng-Chung Wei2,3,4, Fu-Shun Yen5

  • 1School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

BMC Medicine
|October 24, 2025
PubMed
Abstract

Insights

Dipeptidyl peptidase-4 (DPP-4) inhibitors may lower tuberculosis (TB) risk in type 2 diabetes mellitus (T2DM) patients. Longer DPP-4 inhibitor use showed a further reduction in pulmonary TB incidence.

Area of Science:

  • Endocrinology
  • Infectious Diseases
  • Immunology

Background:

  • Diabetes mellitus (DM) elevates tuberculosis (TB) risk and worsens treatment.
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors manage blood sugar and modulate immune responses.
  • Investigating DPP-4 inhibitors' impact on TB risk in type 2 diabetes mellitus (T2DM) is crucial.

Purpose of the Study:

  • To compare pulmonary TB risk between DPP-4 inhibitor users and non-users with T2DM.
  • To assess the association between DPP-4 inhibitor use duration and TB risk.

Main Methods:

  • An emulated target trial using Taiwan's National Health Insurance Research Database (2007-2019).
  • Matched 328,842 pairs of DPP-4 inhibitor users and non-users with T2DM.
  • Cox proportional hazard models and Kaplan-Meier analysis to determine TB risk.

Main Results:

  • DPP-4 inhibitor users had a significantly lower risk of new-onset pulmonary TB (aHR: 0.85, 95% CI: 0.81-0.90).
  • Kaplan-Meier analysis confirmed lower cumulative TB incidence in DPP-4 inhibitor users (p < 0.001).
  • Extended DPP-4 inhibitor use correlated with reduced pulmonary TB risk.

Conclusions:

  • DPP-4 inhibitor use is linked to a significantly lower risk of pulmonary TB in T2DM patients.
  • Longer cumulative duration of DPP-4 inhibitor use may offer further protection against TB.
Keywords:
Cumulative durationDipeptidyl peptidase-4 inhibitorsEmulated target trialPulmonary tuberculosis

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