Tirzepatide and the risk of asthma exacerbations in patients with type 2 diabetes.

BACKGROUND: Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, demonstrates anti-inflammatory properties that may benefit patients with asthma and type 2 diabetes (T2D). We sought to assess the comparative effectiveness of TZP versus other antidiabetic agents in reducing acute asthma exacerbations among patients with concurrent asthma and T2D. METHODS: We conducted a retrospective cohort study using TriNetX US network. Adult patients with asthma and T2D initiating TZP or comparator antidiabetic agents (sulfonylureas [SU], dipeptidyl peptidase-4 inhibitors [DPP4i], sodium-glucose cotransporter 2 inhibitors [SGLT2i], or GLP-1 receptor agonists [GLP-1RA]) between January 2022 and August 2025 were included. Propensity score matching was performed for each comparison. The primary outcome was acute asthma exacerbation and secondary outcome was all-cause mortality. RESULTS: After propensity score matching, we analyzed 25,712 patients in each TZP versus SU cohort, 23,013 in each TZP versus DPP4i cohort, 30,292 in each TZP versus SGLT2i cohort, and 19,740 in each TZP versus GLP-1RA cohort. TZP was associated with lower risk of asthma exacerbations compared with SU (HR, 0.81; 95% CI, 0.72-0.92) and DPP4i (HR, 0.82; 95% CI, 0.72-0.94). No significant differences were observed versus SGLT2i (HR, 1.12; 95% CI, 0.99-1.27; P = .064) or GLP-1RA (HR, 1.06; 95% CI, 0.91-1.23; P = .49). TZP was associated with the lower risk of all-cause mortality compared with SU, DPP4i, and SGLT2i (all P <.001). CONCLUSIONS: Among patients with coexisting asthma and T2D, TZP use was associated with a lower risk of acute asthma exacerbations compared with SU and DPP4i, and was associated with lower all-cause mortality compared with SU, DPP4i, and SGLT2i, but not compared with GLP-1RA.