ArticleFrontiers in pharmacology2026
Tirzepatide versus other glucose-lowering therapies and risk of COPD exacerbations in patients with comorbid type 2 diabetes: a retrospective cohort study.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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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