{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:51:41Z","timestamp":1791525101163,"version":"4.3.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Matched populations included 6,080 patients per group (TZP\u2013SGLT2i), 4,684 (TZP\u2013DPP-4i), and 6,727 (TZP\u2013GLP-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\u20130.82] and 0.72 [95% CI 0.63\u20130.82], respectively) and all-cause mortality (HR 0.30 [95% CI 0.23\u20130.38] and 0.24 [95% CI 0.18\u20130.31], 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\u20130.72]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1917340","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:29:58Z","timestamp":1791523798000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tirzepatide versus other glucose-lowering therapies and risk of COPD exacerbations in patients with comorbid type 2 diabetes: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Wan-Hsuan","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-En","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jheng-Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"Department of Public Health, College of Medicine, National Cheng Kung University","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Ming","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yu","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Wen","family":"Shiau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.3390\/jcm14061809","article-title":"Chronic obstructive pulmonary disease and type 2 diabetes mellitus: complex interactions and clinical implications","volume":"14","author":"Anghel","year":"2025","journal-title":"J. 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