Comparative Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors on Sepsis in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study
8 affiliations
- 1School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taitung MacKay Memorial Hospital, Taitung, Taiwan
- 3Department of Medicine, MacKay Medical University, New Taipei City, Taiwan
- 4World Wise Executive Leadership Program, Minerva University, San Francisco, CA, USA
- 5Division of Pulmonary Medicine, Department of Internal Medicine, Cardinal Tien Hospital, and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- 6Medical Research Center, Cardinal Tien Hospital, and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- 7Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- 8School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
Abstract
Background: Sepsis is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Antihyperglycemic agents may influence infection risk through distinct immunometabolic pathways. We compared glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with COPD and type 2 diabetes mellitus (T2DM).
Methods: This population-based, active-comparator, new-user cohort study used the TriNetX Global Network. Adults aged 40–100 years with COPD and T2DM who initiated a GLP-1RA or DPP-4i between 2007 and 2019 were included. Propensity score matching (1:1) adjusted for demographics, BMI, HbA1c, COPD severity proxies, comorbidities, and medications. The primary outcome was sepsis; secondary outcomes were pneumonia, severe sepsis, and all-cause mortality, assessed at 1, 3, 6, 12, and 24 months.
Results: Before matching, 21,622 patients started a GLP-1RA and 67,259 a DPP-4i; after matching, 20,074 remained in each group with balanced characteristics (all standardized mean differences <0.10). Compared with DPP-4i users, GLP-1RA users had a significantly lower risk of sepsis at 1 year (hazard ratio [HR] 0.852; 95% confidence interval [CI] 0.770–0.942). The risks of secondary outcomes at 1 year were numerically lower in the GLP-1RA group, with statistically significant reductions in pneumonia (HR 0.729; 95% CI 0.671–0.792) and all-cause mortality (HR 0.656; 95% CI 0.587–0.732), while the association with severe sepsis did not reach statistical significance (HR 0.891; 95% CI 0.770–1.033).
Conclusion: In patients with COPD and T2DM, initiation of GLP-1RAs was associated with lower risks of sepsis, pneumonia, and all-cause mortality compared with DPP-4is. However, given the observational design, causality cannot be established and residual confounding remains a potential limitation. While these findings suggest potential benefits of GLP-1RAs beyond glycemic control, further confirmation through randomized controlled trials is warranted to guide clinical decision-making.
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BibTeX
@article{wu2026comparative,
title = {{Comparative Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors on Sepsis in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study}},
author = {Ting-Jia Wu and Chao-Hsien Chen and Hsiu-Chin Wu and Ya-Hui Wang and Cheng-Yi Wang and Chih-Cheng Lai},
journal = {International Journal of Chronic Obstructive Pulmonary Disease},
year = {2026},
month = oct,
doi = {10.2147/copd.s602087},
url = {https://doi.org/10.2147/copd.s602087},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Comparative Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors on Sepsis in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study
AU - Ting-Jia Wu
AU - Chao-Hsien Chen
AU - Hsiu-Chin Wu
AU - Ya-Hui Wang
AU - Cheng-Yi Wang
AU - Chih-Cheng Lai
PY - 2026
DA - 2026/10/30
JO - International Journal of Chronic Obstructive Pulmonary Disease
DO - 10.2147/copd.s602087
UR - https://doi.org/10.2147/copd.s602087
AB - Background: Sepsis is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Antihyperglycemic agents may influence infection risk through distinct immunometabolic pathways. We compared glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with COPD and type 2 diabetes mellitus (T2DM). Methods: This population-based, active-comparator, new-user cohort study used the TriNetX Global Network. Adults aged 40–100 years with COPD and T2DM who initiated a GLP-1RA or DPP-4i between 2007 and 2019 were included. Propensity score matching (1:1) adjusted for demographics, BMI, HbA1c, COPD severity proxies, comorbidities, and medications. The primary outcome was sepsis; secondary outcomes were pneumonia, severe sepsis, and all-cause mortality, assessed at 1, 3, 6, 12, and 24 months. Results: Before matching, 21,622 patients started a GLP-1RA and 67,259 a DPP-4i; after matching, 20,074 remained in each group with balanced characteristics (all standardized mean differences <0.10). Compared with DPP-4i users, GLP-1RA users had a significantly lower risk of sepsis at 1 year (hazard ratio [HR] 0.852; 95% confidence interval [CI] 0.770–0.942). The risks of secondary outcomes at 1 year were numerically lower in the GLP-1RA group, with statistically significant reductions in pneumonia (HR 0.729; 95% CI 0.671–0.792) and all-cause mortality (HR 0.656; 95% CI 0.587–0.732), while the association with severe sepsis did not reach statistical significance (HR 0.891; 95% CI 0.770–1.033). Conclusion: In patients with COPD and T2DM, initiation of GLP-1RAs was associated with lower risks of sepsis, pneumonia, and all-cause mortality compared with DPP-4is. However, given the observational design, causality cannot be established and residual confounding remains a potential limitation. While these findings suggest potential benefits of GLP-1RAs beyond glycemic control, further confirmation through randomized controlled trials is warranted to guide clinical decision-making.
SN - 1176-9106
SN - 1178-2005
ER -