Tirzepatide vs semaglutide for asthma: the difference was smaller than researchers expected

by · News-Medical

Researchers compared two widely used incretin therapies in more than 16,000 matched adults with asthma and type 2 diabetes, tracking exacerbations and asthma medication prescriptions over 12 months.

Study: Association of Tirzepatide versus Semaglutide with Risk of Asthma Exacerbation in Patients with Asthma and Type 2 Diabetes: A US Multicenter Retrospective Cohort Study. Image Credit: antoniodiaz / Shutterstock

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Background

About 13%–16% of people with asthma also have T2D, and this combination is associated with poorer asthma control, more frequent and severe exacerbations, and greater healthcare utilization.

Obesity can worsen asthma by promoting airway hyperreactivity, impairing lung mechanics, and contributing to corticosteroid resistance, while poor glycemic control can exacerbate airway inflammation and increase asthma exacerbation risk.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), lowers glucose and reduces weight, while tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA with greater effects on weight and glycemic control.

Preclinical evidence suggests incretin therapies may affect airway inflammation and bronchial hyperresponsiveness, but comparative respiratory evidence remains limited.

About the study

Electronic health record (EHR) data from the TriNetX United States (US) Collaborative Network were used in a retrospective cohort study with a new-user, active-comparator design.

New users had no prior use of GLP-1 RAs or GIP/GLP-1 RAs during the preceding year. Patients with type 1 or gestational diabetes, chronic obstructive pulmonary disease (COPD), or missing body mass index (BMI) or hemoglobin A1c (HbA1c) were excluded.

Diagnoses were identified using the International Classification of Diseases, Tenth Revision (ICD-10) codes, while prescriptions were identified using the Anatomical Therapeutic Chemical (ATC) classification system and RxNorm codes.

The primary outcome was time to the first asthma exacerbation over 12 months. Secondary outcomes were time to the first prescription of systemic corticosteroids or a short-acting beta-agonist (SABA).

Covariates included demographics, smoking status, BMI, HbA1c, comorbidities, and medications, including long-acting beta2 agonists (LABAs). A 1:1 propensity score matching (PSM) balanced groups.

Standardized mean difference (SMD) was reported as absolute standardized mean difference (aSMD). Kaplan-Meier and log-rank tests were used, and Cox models were used to compare outcomes between the treatment groups.

Study results

Among 455,196 adults with asthma and T2D, 8,178 tirzepatide users and 28,135 semaglutide users met the study eligibility criteria. After 1:1 PSM, 8,176 patients remained in each group.

Before matching, tirzepatide users included a higher proportion of White patients and a lower proportion of Black or African American patients than semaglutide users. After matching, baseline characteristics were well balanced. Mean follow-up was 352.2 days for tirzepatide and 355.4 days for semaglutide users.

The main analysis found no difference in the risk of asthma exacerbation between treatments. Asthma exacerbations occurred in 11.0% of tirzepatide users and 11.1% of semaglutide users.

Kaplan-Meier analyses supported this finding, and the results remained consistent across different follow-up durations. Similar exacerbation risks were observed at both 6 and 18 months and when the new-user washout period was extended from 1 year to 2 years.

Subgroup analyses showed no difference in asthma exacerbation risk between tirzepatide and semaglutide across baseline BMI, HbA1c, heart failure (HF), chronic kidney disease (CKD), prednisone use, or previous asthma exacerbation.

Results were also consistent across the sensitivity and subgroup analyses. Formal interaction testing was not performed, so the study could not determine whether treatment effects differed between subgroups.

For secondary outcomes, tirzepatide was associated with a lower likelihood of receiving a SABA prescription than semaglutide. The risk of receiving a systemic corticosteroid prescription was similar between groups. Asthma exacerbation risk was similar between treatments, while tirzepatide was associated with a lower likelihood of receiving a SABA prescription.

The authors noted that tirzepatide's greater weight reduction and glycemic improvement did not translate into a differential reduction in asthma exacerbations. They suggested that the metabolic improvements achieved during the one-year follow-up may have been insufficient to meaningfully affect the risk of exacerbations.

Limitations included possible residual confounding, the lack of direct measures of asthma severity, prescription-based exposure measurement, treatment switching or discontinuation not being accounted for, possible misclassification of asthma exacerbations using ICD-10 codes, inability to distinguish exacerbation severity, and possible selection bias from excluding patients with missing BMI or HbA1c.

Conclusions

Among adults with asthma and T2D, tirzepatide and semaglutide were associated with similar risks of asthma exacerbation. This result remained consistent across different follow-up periods, a longer new-user washout period, and subgroups defined by BMI, HbA1c, HF, CKD, prednisone use, and previous exacerbation.

Given the observational nature of the study and the potential for residual confounding and outcome misclassification, the findings should be interpreted cautiously. Randomized controlled trials are warranted to clarify the comparative effects of these therapies on asthma outcomes.

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