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Association of Glucagon-Like Peptide-1 Receptor Agonists With Optic Nerve and Retinal Adverse Events: A

Moiz Lakhani1, Angela T H Kwan1, Andrew Mihalache2

  • 1From the Faculty of Medicine (M.L., A.T.H.K.), University of Ottawa, Ottawa, Ontario, Canada; The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada.

American Journal of Ophthalmology
|May 18, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide are linked to increased risks of serious eye conditions, including ischemic optic neuropathy and diabetic retinopathy. Post-marketing surveillance is crucial for monitoring these ophthalmic safety concerns.

Area of Science:

  • Pharmacovigilance and Ophthalmology
  • Endocrinology and Diabetes Management
  • Drug Safety and Therapeutics

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity.
  • Concerns regarding the ophthalmic safety of GLP-1 RAs necessitate thorough investigation.
  • Understanding potential ocular adverse events (AEs) is critical for patient care.

Purpose of the Study:

  • To investigate the association between GLP-1 RAs, specifically semaglutide and tirzepatide, and ocular adverse events.
  • To analyze reported cases of optic nerve and retinal conditions linked to these medications.
  • To assess the ophthalmic safety profile of semaglutide and tirzepatide in a real-world setting.

Main Methods:

  • A global observational pharmacovigilance study utilizing the US FAERS and WHO's VigiBase databases.
  • Analysis of ocular AEs associated with semaglutide and tirzepatide from their approval dates through September 2024.
  • Disproportionality analyses using reporting odds ratios (RORs) with comparisons to other drugs and comparators like metformin, empagliflozin, dulaglutide, and insulin.

Main Results:

  • Semaglutide demonstrated significantly higher odds of ischemic optic neuropathy (ION) and diabetic retinopathy (DR) across both databases.
  • Associations were also found between semaglutide and retinal/vitreous detachment, hemorrhage, and tear.
  • Tirzepatide was significantly associated with DR in the FAERS database, while other ocular AEs were less consistently reported.

Conclusions:

  • The widespread use of semaglutide necessitates heightened awareness of its association with ocular adverse events.
  • Robust global pharmacovigilance and ongoing post-marketing surveillance are essential for monitoring the ophthalmic safety of GLP-1 RAs.
  • Further research may be warranted to elucidate the mechanisms underlying these observed associations.

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