BACKGROUND AND PURPOSE:

• There are anecdotal reports that associate semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), with nonarteritic anterior ischemic optic neuropathy (NAION)
• Hathaway et al. (JAMA Ophthalmology, 2024) investigated whether there is an association between semaglutide and risk of NAION

METHODS:

• Retrospective matched cohort study
• Population
  • Patients with type 2 diabetes (T2D) or overweight/obesity
  • No history of NAION
• Exposures
  • Semaglutide
  • Non-GLP-1 RA medications
• Study design
  • Participants using semaglutide were propensity score-matched to those who did not use semaglutideCovariates that were addressed
    • Sex | Age | Systemic hypertension | T2D | Obstructive sleep apnea | Obesity | Hyperlipidemia | Coronary artery disease | Contraindications for use of semaglutide
  • The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities
• Primary outcomes
  • Cumulative incidence and hazard ratio (HR) of NAION

RESULTS:

• 16,827 patients
  • With T2D: 710
    • Semaglutide: 194 | Non-GLP-1 RA medication: 516
    • Median age: 59 (IQR, 49 to 68) | 52% female
  • With overweight or obesity: 979
    • Semaglutide: 361 | Non-GLP-1 RA medication: 618
    • Median age: 47 (IQR, 32 to 59) | 72% female

In the T2D Population

• Cumulative incidence of NAION
  • Semaglutide: 8.9% (95% CI, 4.5 to 13.1)
  • Non-GLP-1 RA medication: 1.8% (95% CI, 0 to 3.5)
• There was a higher risk of NAION in patients receiving semaglutide
  • HR 4.28 (95% CI, 1.62 to 11.29) | P<0.001

In the Overweight/Obesity Population

• Cumulative incidence of NAION
  • Semaglutide: 6.7% (95% CI, 3.6 to 9.7)
  • Non-GLP-1 RA medication: 0.8% (95% CI, 0 to 1.8)
• There was a higher risk of NAION in patients receiving semaglutide in this population as well
  • HR 7.64 (95% CI, 2.21 to 26.36) | P<0.001

CONCLUSION:

• Semaglutide is associated with a higher risk of NAION
• The authors state

This study is the first, to our knowledge, to report an association between semaglutide and NAION, although the design of our study did not enable query into a causal relationship between the two

The best approaches to confirm, refute, or refine our findings would be to conduct a much larger, retrospective, multicenter population-based cohort study; a prospective, randomized clinical study; or a postmarket analysis of all GLP-1 RA drugs

Learn More – Primary Sources:

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide