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Ocular complications from glucagon-like peptide-1 receptor agonists: Clinical evidence, potential mechanisms, and

Tzu-En Wu1, Harn-Shen Chen2,3

  • 1Department of Ophthalmology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC.

Journal of the Chinese Medical Association : JCMA
|March 20, 2026
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer diabetes benefits but may pose ocular risks, particularly diabetic retinopathy complications in high-risk patients. Careful monitoring is crucial for managing these potential adverse effects.

Area of Science:

  • Endocrinology
  • Ophthalmology
  • Pharmacology

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are vital for type 2 diabetes mellitus (T2DM) management, offering glycemic, weight, cardiovascular, and renal benefits.
  • Emerging evidence suggests a concerning ocular safety profile associated with GLP-1 RA use, particularly regarding diabetic retinopathy (DR).

Purpose of the Study:

  • To comprehensively review the ocular safety profile of GLP-1 RAs, focusing on diabetic retinopathy and other adverse events.
  • To synthesize findings from clinical trials, observational studies, and pharmacovigilance reports regarding GLP-1 RAs and ocular complications.

Main Methods:

  • Analysis of clinical trial data (e.g., SUSTAIN-6, REWIND, LEADER) examining DR incidence and progression.
  • Review of observational studies and meta-analyses investigating DR risk compared to other diabetes treatments.
  • Evaluation of pharmacoepidemiologic studies and pharmacovigilance reports on nonarteritic anterior ischemic optic neuropathy (NAION) and other retinal disorders.

Main Results:

  • Clinical trials show mixed results for DR, with some indicating increased complications (e.g., semaglutide in SUSTAIN-6) especially with rapid HbA1c reduction in pre-existing DR, while others show no significant effect.
  • Observational data on DR risk are inconsistent, with some studies suggesting higher risk in vulnerable groups and others lower risk than insulin.
  • Reports link GLP-1 RAs, particularly semaglutide, to NAION, classified as a rare adverse effect, while some real-world data suggest potential protection against neovascular age-related macular degeneration and diabetic macular edema.

Conclusions:

  • GLP-1 RAs present a complex ocular safety profile, with risks potentially concentrated in specific patient subgroups, such as those with pre-existing DR.
  • Mechanisms may involve rapid metabolic shifts, vascular changes, or direct tissue effects, necessitating further research.
  • Individualized prescribing, baseline ophthalmic evaluation, and interdisciplinary monitoring are recommended to mitigate potential ocular risks associated with GLP-1 RA therapy.
Keywords:
Diabetic retinopathyGlucagon-like peptide-1 receptor agonistsNeovascular age-related macular degenerationNonarteritic anterior ischemic optic neuropathy

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