Glucagon-like-peptide-1 Receptor Agonists (GLP-1 RAs) and the Ear

Erika McCarty Walsh, MD, Chair, Otology and Neurotology Education Committee

Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) are everywhere—in the media and on our patients’ medication lists. In a 2024 KFF poll, one in eight American adults report having ever taken a GLP-1 RA.¹ These drugs promote pancreatic insulin secretion, decrease glucagon secretion, and delay gastric emptying to reduce blood glucose and promoting weight loss.² The first GLP-1 RA approved by the United States Food and Drug Administration (FDA) for type II diabetes mellitus was exenatide in 2005. Perhaps just as important as their effect on blood glucose is their promise in treating obesity, and the first GLP-1 RA approval for treatment of obesity was granted in 2014 (liraglutide).³  As the number of patients on these important medications has increased, more attention is being paid to the potential short- and long-term otologic side effects of these drugs.

A recent analysis by Khan et al of the FDA Adverse Event Reporting System (FAERS), which collects data on drugs after FDA approval, suggested a possible relationship between certain medications in the GLP-1 RA class and tinnitus, hearing loss, and vertigo. However, the strength of this association was weak when compared to the association of GLP-1 RAs with common, well-established side effects, like gastroesophageal reflux.⁴ In another network meta-analysis of GLP-1 RA randomized controlled trials, only two GLP-1 RAs showed a higher association with hearing loss than control. Importantly, these medications, lixisenatide and efpeglenatide, are not currently available in the U.S.⁵ Note that these associations were not class-wide, and more research is needed to understand the relationship between these common otologic complaints and GLP-1 RA use, including formal studies using standardized audiometric measures.

Patulous Eustachian tube has long been associated with significant weight loss. In patulous Eustachian tube, the Eustachian tube no longer functions as a dynamic valve and is instead perpetually open. Patients report autophony and aural fullness, and movement of the tympanic membrane may be seen with nasal breathing. On nasopharyngoscopy, the torus tubarius may appear thin and atrophic, and the Eustachian tube orifice will be easily visible. In weight loss, loss of tissue at the fat pads of Ostmann is theorized to result in patulous Eustachian tube.⁶ Pak et al report on two patients with patulous Eustachian tube after GLP-1 RA use and present their analysis of the FAERS data. The prevalence of otologic side effects in the FAERS was 0.99%, mostly reports of decreased hearing and vertigo.⁷ However, there was insufficient data to conclude how common patulous Eustachian tube may be in patients receiving GLP-2 RAs.

Despite concerns about possible negative side effects of GLP-1 RAs, they may hold some promise in otologic disease. Preliminary data suggest a possible neurotrophic and neuroprotective benefit of these medications. In an chinchilla model of acoustic blast injury, treatment with liraglutide decreased the severity of blast-induced hearing loss.⁸ Whether these results could translate to the human inner ear is unclear, but this is an exciting avenue of ongoing investigation.

References

1. Montero A, Sparks G, Presiado M, Hamel L. KFF Health Tracking Poll May 2024: The Public’s Use and Views of GLP-1 Drugs.
2. Yao H, Zhang A, Li D, et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ. 2024;384:e076410. doi:10.1136/bmj-2023-076410
3. Drucker DJ, Habener JF, Holst JJ. Discovery, characterization, and clinical development of the glucagon-like peptides. J Clin Invest. 2017;127(12):4217-4227. doi:10.1172/JCI97233
4. Khan FI, Vazquez SGS, Mehdi Z, et al. Otolaryngologic Side Effects of GLP-1 Receptor Agonists. Laryngoscope. 2025;135(7):2291-2298. doi:10.1002/lary.32061
5. Chen JJ, Hsu CW, Hung CM, et al. Risk of Hearing Loss in Patients Treated with Exendin-4 Derivatives: A Network Meta-Analysis of Glucagon-like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors. Pharmaceuticals (Basel). 2025;18(5):735. doi:10.3390/ph18050735
6. Poe DS. Diagnosis and management of the patulous eustachian tube. Otol Neurotol. 2007;28(5):668-677. doi:10.1097/mao.0b013e31804d4998
7. Pak KY, Cutri RM, Nadeem W, et al. GLP-1 Receptor Agonist Induced Eustachian Tube Dysfunction: Database and Systematic Review of Otolaryngologic Adverse Events. Otol Neurotol. 2025;46(1):19-22. doi:10.1097/MAO.0000000000004373
8. Jiang S, Welch P, Sanders S, Gan RZ. Mitigation of Hearing Damage After Repeated Blast Exposures in Animal Model of Chinchilla. J Assoc Res Otolaryngol. 2022;23(5):603-616. doi:10.1007/s10162-022-00862-2