J Diabetes Sci Technol

Evidence update: Semaglutide doesn’t appear to be linked to NAION risk

August 6, 2024

After controlling for confounders in seven real-world analyses, no significant increase in risk of nonarteritic anterior ischemic optic neuropathy (NAION) was observed for semaglutide or any GLP-1RA.

• Noting that the single-site nature of the recent study and possibility of residual confounding where the clinical course of patients seen at an ophthalmology clinical might not be generalizable to the general population, Stanford researchers performed seven retrospective real-world cohort analyses of adult users of GLP-1RA drugs for diabetes and obesity. Studies were done utilizing high-dimensional propensity score matching to control for confounders and were performed on a 66 million patient nationally representative EHR and claims dataset, rather than a single ophthalmology clinic database.
• The primary analysis included adults who initiated GLP-1RA weight loss medications vs. non-GLP-1 agonist weight loss medications without a prior history of NAOIN. A model evaluating time to develop NAION showed increased risk in the GLP-1RA arm prior to adjusting for comorbidities (hazard ratio [HR], 2.95; 95% CI, 1.82-4.79; P < .0001), but the difference was eliminated after controlling for confounders (HR, 1.45; 95% CI, 0.51-4.17; P = .49).
• Five sensitivity analyses were performed on the national data including limiting the GLP-1RA arm to only semaglutide (as evaluated in the prior study), limiting cohorts to patients with T2DM or with obesity, and only evaluating patients with a definitive ophthalmologic exam in the post-treatment follow-up period.
• The primary study protocol was also replicated within the Stanford Healthcare research repository (N=3.9 million patients) where a similar association was seen prior to matching but eliminated after matching.
• Frequency of NAION in the analyses ranged from 0.07% to 0.24%.

Source:

Klonoff DC, at al. (2024, July 29). J Diabetes Sci Technol. Real-World Evidence Assessment of the Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. https://pubmed.ncbi.nlm.nih.gov/39080859/