GLP-1 Receptor Agonist Effect on Disease Severity in Idiopathic Subglottic Stenosis

Clinical Question

Does GLP-1 receptor agonist (GLP-1RA) therapy prolong the surgery-free interval in patients with idiopathic subglottic stenosis (iSGS), independent of weight loss?

Bottom Line

In this single-center retrospective cohort, initiation of GLP-1RA therapy was associated with an increase in surgery-free interval (SFI), from 15.0 to 25.7 months, among iSGS patients. This effect did not correlate with weight loss or baseline body mass index (BMI), suggesting a potential disease-modifying, anti-inflammatory impact of GLP-1RAs beyond their metabolic benefits.

Background: Idiopathic subglottic stenosis is a rare condition of progressive airway narrowing that occurs almost exclusively in middle-aged women and is typically managed with serial airway dilations, imposing substantial healthcare burden. Systemic inflammatory dysregulation, including activation of the IL 17A/IL 23 axis and PD-1 pathways, is implicated in iSGS pathogenesis. GLP-1RAs, widely used for diabetes and weight loss, have demonstrated systemic anti-inflammatory effects and benefit across several immune-mediated diseases, raising interest in their potential role in airway stenosis.

Study Design: Retrospective cohort study of 223 iSGS patients treated between 2013 and 2025, identifying those prescribed GLP-1RAs. Patients were included if GLP-1RA was listed as active in their electronic health record. Patients were excluded if GLP 1RAs were started before a baseline surgery-free interval (SFI) was established or if they received serial intralesional steroid injections, endoscopic or open cricotracheal resection. For eligible patients, the investigators analyzed pre- and post-therapy SFI, normalized SFI, weight loss, BMI, and Cotton-Myer grade using paired t-tests, linear regressions, and a generalized linear mixed effects model.

Setting: Single tertiary academic otolaryngology center—Johns Hopkins Hospital, Baltimore

Synopsis: Among 223 iSGS patients, 32 (14%) were on GLP-1RAs, and 14 met inclusion criteria. All patients were female, with a mean age of 48.9 years and predominantly class II–III obesity. Patients underwent an average of 4.5 dilations over 53.7 months before GLP-1RA initiation and were on therapy for a mean of 21.9 months. Mean SFI increased from 15.0 to 25.7 months after starting GLP-1RAs, yielding a normalized SFI of 1.69 (≈68.5% increase). All but three patients had longer SFIs. Patients lost an average of 39 pounds, with BMI decreasing from 39.0 to 32.2. However, multiple and univariate linear regression showed no meaningful association between SFI change and weight loss or initial BMI.

Cotton-Myer grade at the time of dilation remained unchanged, indicating that patients presented with similar disease severity at the time of dilation rather than more severe disease.

The authors interpret these findings as consistent with a GLP-1RA-mediated anti-inflammatory effect on iSGS, potentially reducing recurrence and healthcare burden, while acknowledging limitations of the small sample size, retrospective design, and the need to assess durability and mechanistic pathways in larger cohorts.

Citation: Malka RE, et al. GLP-1 receptor agonist effect on disease severity in idiopathic subglottic stenosis. Otolaryngol Head Neck Surg. 2026. https://doi.org/10.1002/ohn.70327.