Association of Glucagon-Like Peptide-1 Receptor Analogues and Laryngeal Symptoms in Obese Adults.
GLP-1RA therapy is associated with a higher risk of laryngeal symptoms, particularly cough and voice disorders, although the absolute risk increases are small.
Where it sits
this study against the rest of the albiglutide corpusSummary and findings
This study investigated the association between glucagon-like peptide-1 receptor analogues (GLP-1RAs) and laryngeal symptoms in obese adults. A total of 617,296 adults on GLP-1RA medications were compared with 3,503,102 controls. The findings indicated an increased risk of laryngeal manifestations associated with GLP-1RA therapy.
Abstract
<h4>Objectives</h4>Given the unprecedented rise in glucagon-like peptide-1 receptor analogue (GLP-1RA) therapy over the past decade, we aimed to investigate potential unintended laryngeal manifestations.<h4>Methods</h4>A retrospective cohort study was conducted using the TriNetX United States Collaborative Network. Adults with obesity on GLP-1RA medications (n = 617,296) from January 1, 2016 to December 3, 2025, were compared with controls (n = 3,503,102), excluding patients with head and neck neoplasms, head and neck radiation therapy, autoimmune diseases, airway disorders or acute respiratory conditions via ICD-10 and CPT codes. Laryngeal symptoms within 1, 3, and 6 months of initiation of GLP-1RA were assessed in propensity score-matched cohorts by age, sex, race, and ethnicity. Outcomes were reported as risk differences (RD) and odds ratios (OR) with 95% confidence intervals (CI).<h4>Results</h4>GLP-1RA therapy increased the 6-month risk of any laryngeal manifestations (OR 1.19, 95% CI 1.16-1.21; p < 0.0001). Higher odds were observed for cough (OR 1.46, p < 0.0001), foreign body sensation (OR 1.1.41, p < 0.001), and voice and resonance disorders (OR 1.19, p = 0.002). Across agents, exenatide, liraglutide, semaglutide, dulaglutide, and lixisenatide showed significant elevated 6-month risk of laryngeal manifestations (OR 1.16-1.91-1.48; p < 0.05), while albiglutide and tirzepatide did not.<h4>Conclusion</h4>GLP-1RA/GIP use in adults is linked to higher rates of laryngeal symptoms, most notably cough and voice and resonance disorders. While absolute risk differences were small, the large number of affected individuals underscores the potential clinical and public health relevance of these findings, in the context of the rapidly growing prevalence of GLP-1RA/GIP use.<h4>Level of evidence: 3</h4>
Background
This paper addresses the potential unintended laryngeal manifestations associated with glucagon-like peptide-1 receptor analogue (GLP-1RA) therapy, which has seen increased use in recent years. Prior knowledge indicated that GLP-1RAs are effective for weight management and glycemic control, but less was known about their impact on laryngeal health. Understanding these associations is essential given the rising prevalence of GLP-1RA therapy and its implications for patient care.
Methods
A retrospective cohort study was conducted using the TriNetX United States Collaborative Network. The study included 617,296 adults with obesity on GLP-1RA medications and 3,503,102 controls, excluding patients with certain conditions. Laryngeal symptoms were assessed at 1, 3, and 6 months post-initiation of GLP-1RA therapy, using propensity score matching for demographic factors.
Results
The primary finding was an increased risk of any laryngeal manifestations at 6 months, with an odds ratio (OR) of 1.19 (95% CI 1.16-1.21; p<0.0001). Specific symptoms such as cough (OR 1.46, p<0.0001), foreign body sensation (OR 1.41, p<0.001), and voice and resonance disorders (OR 1.19, p=0.002) were also significantly elevated. Notably, albiglutide and tirzepatide did not show significant increased risk.
Interpretation
The results suggest a statistically significant association between GLP-1RA therapy and laryngeal symptoms, which aligns with some prior literature indicating potential side effects of these medications. However, the effect sizes, while statistically significant, may not be clinically meaningful given the small absolute risk differences. Limitations include the retrospective nature of the study and potential confounding factors inherent in observational designs.
Key findings
- OR 1.19 for any laryngeal manifestations at 6 months, 95% CI 1.16-1.21, p<0.0001.
- OR 1.46 for cough at 6 months, p<0.0001.
- OR 1.41 for foreign body sensation at 6 months, p<0.001.
- OR 1.19 for voice and resonance disorders at 6 months, p=0.002.
- OR for exenatide, liraglutide, semaglutide, dulaglutide, and lixisenatide ranged from 1.16 to 1.91, p<0.05.
- Albiglutide and tirzepatide did not show significant increased risk.
Limitations
- retrospective cohort study design
- small absolute risk differences despite statistical significance
- potential confounding factors not controlled for
- exclusion of certain patient populations may limit generalizability