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Peer-reviewedCC BYFrontiers in pharmacology

Tirzepatide versus other glucose-lowering therapies and risk of COPD exacerbations in patients with comorbid type 2 diabetes: a retrospective cohort study

  • Wan-Hsuan Hsu1
  • Yang-En Chan2
  • Jheng-Yan Wu3
  • Yao-Ming Chuang2
  • Chia-Yu Kuo2
  • Bo-Wen Shiau1
  • Po-Yu Huang1
  • Chih-Cheng Lai4
4 affiliations
  1. 1Department of Internal Medicine, Chi Mei Medical Center , ,
  2. 2Department of General Medicine, Chi Mei Medical Center , ,
  3. 3Department of Nutrition, Chi Mei Medical Center , ,
  4. 4Department of Intensive Care Medicine, Chi Mei Medical Center , ,
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Abstract

Background: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) frequently coexist, sharing inflammatory and metabolic pathways. Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has demonstrated metabolic and anti-inflammatory effects. However, its impact on pulmonary outcomes in patients with COPD and T2D remains uncertain.

Methods: Using the TriNetX global research network, we conducted a retrospective cohort study of adults with coexisting COPD and T2D prescribed TZP, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), or glucagon-like peptide-1 receptor agonists (GLP-1RA). Propensity score matching (1:1) was performed separately for each comparison. Primary outcome was COPD exacerbation; secondary outcomes included all-cause mortality, acute respiratory failure, and lower respiratory tract infection. Outcomes were assessed during a prespecified observation period from day one through day 365 after the index date.

Results: Matched populations included 6,080 patients per group (TZP–SGLT2i), 4,684 (TZP–DPP-4i), and 6,727 (TZP–GLP-1RA). In the independently matched comparisons, median follow-up was 232 versus 365 days for TZP versus SGLT2i, 235 versus 365 days for TZP versus DPP-4i, and 233 versus 365 days for TZP versus other GLP-1RAs; incidence rates were expressed per 1,000 person-years. Compared with SGLT2i and DPP-4i, TZP significantly reduced COPD exacerbation risk (hazard ratio [HR] 0.73 [95% CI 0.64–0.82] and 0.72 [95% CI 0.63–0.82], respectively) and all-cause mortality (HR 0.30 [95% CI 0.23–0.38] and 0.24 [95% CI 0.18–0.31], respectively). TZP also reduced acute respiratory failure and lower respiratory tract infection risks. Outcomes were similar between TZP and GLP-1RA, except TZP showed lower mortality (HR 0.55 [95% CI 0.42–0.72]).

Conclusion: Among patients with COPD and T2D, TZP use was associated with lower risks of COPD exacerbations, respiratory complications, and mortality compared with SGLT2i and DPP-4i, findings that warrant confirmation through randomized clinical trials.

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Cite

BibTeXRIS
BibTeX
@article{hsu2026tirzepatide,
  title = {{Tirzepatide versus other glucose-lowering therapies and risk of COPD exacerbations in patients with comorbid type 2 diabetes: a retrospective cohort study}},
  author = {Wan-Hsuan Hsu and Yang-En Chan and Jheng-Yan Wu and Yao-Ming Chuang and Chia-Yu Kuo and Bo-Wen Shiau and Po-Yu Huang and Chih-Cheng Lai},
  journal = {Frontiers in pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1917340},
  url = {https://europepmc.org/article/PMC/PMC13690786},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Tirzepatide versus other glucose-lowering therapies and risk of COPD exacerbations in patients with comorbid type 2 diabetes: a retrospective cohort study
AU  - Wan-Hsuan Hsu
AU  - Yang-En Chan
AU  - Jheng-Yan Wu
AU  - Yao-Ming Chuang
AU  - Chia-Yu Kuo
AU  - Bo-Wen Shiau
AU  - Po-Yu Huang
AU  - Chih-Cheng Lai
PY  - 2026
DA  - 2026/10/09
JO  - Frontiers in pharmacology
DO  - 10.3389/fphar.2026.1917340
UR  - https://europepmc.org/article/PMC/PMC13690786
AB  - Background: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) frequently coexist, sharing inflammatory and metabolic pathways. Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has demonstrated metabolic and anti-inflammatory effects. However, its impact on pulmonary outcomes in patients with COPD and T2D remains uncertain.  Methods: Using the TriNetX global research network, we conducted a retrospective cohort study of adults with coexisting COPD and T2D prescribed TZP, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), or glucagon-like peptide-1 receptor agonists (GLP-1RA). Propensity score matching (1:1) was performed separately for each comparison. Primary outcome was COPD exacerbation; secondary outcomes included all-cause mortality, acute respiratory failure, and lower respiratory tract infection. Outcomes were assessed during a prespecified observation period from day one through day 365 after the index date.  Results: Matched populations included 6,080 patients per group (TZP–SGLT2i), 4,684 (TZP–DPP-4i), and 6,727 (TZP–GLP-1RA). In the independently matched comparisons, median follow-up was 232 versus 365 days for TZP versus SGLT2i, 235 versus 365 days for TZP versus DPP-4i, and 233 versus 365 days for TZP versus other GLP-1RAs; incidence rates were expressed per 1,000 person-years. Compared with SGLT2i and DPP-4i, TZP significantly reduced COPD exacerbation risk (hazard ratio [HR] 0.73 [95% CI 0.64–0.82] and 0.72 [95% CI 0.63–0.82], respectively) and all-cause mortality (HR 0.30 [95% CI 0.23–0.38] and 0.24 [95% CI 0.18–0.31], respectively). TZP also reduced acute respiratory failure and lower respiratory tract infection risks. Outcomes were similar between TZP and GLP-1RA, except TZP showed lower mortality (HR 0.55 [95% CI 0.42–0.72]).  Conclusion: Among patients with COPD and T2D, TZP use was associated with lower risks of COPD exacerbations, respiratory complications, and mortality compared with SGLT2i and DPP-4i, findings that warrant confirmation through randomized clinical trials.
SN  - 1663-9812
ER  -