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Background <p>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).</p> Methods <p>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.</p> Results <p>The follow-up duration was 5.06&#xa0;years for DPP-4 inhibitor users and 4.05&#xa0;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, <i>p</i> &lt; 0.001).</p> <p>Furthermore, a longer cumulative duration of DPP-4 inhibitor use was associated with a lower risk of pulmonary TB.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月24日

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  • Yi-Geng Chen,
  • James Cheng-Chung Wei,
  • Fu-Shun Yen,
  • Chen-Yu Sung,
  • Yu-Han Huang,
  • Teng-Shun Yu,
  • Fuu-Jen Tsai,
  • Chii-Min Hwu,
  • Chih-Cheng Hsu

摘要

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.