The primary objective of this study is to systematically evaluate and analyse existing literature to establish an association between the use of Semaglutide and the development of Non-Arteritic Anterior Ischaemic Optic Neuropathy (NAION). 

Semaglutide (a GLP-1 RA) is primarily approved for treatment for people with type 2 diabetes and, increasingly, for adults with obesity. NAION is a rare but possibly vision threatening syndrome caused by ischaemia of the head of the optic nerve. The earlier reports have shown a 2-3 fold increased risk of NAION in individuals taking Semaglutide. A need to conduct a systematic synthesis of evidence therefore exists to appraise the current evidence, summarise the findings in various populations, and identify knowledge gaps related to this emerging risk.

We reviewed 23 manuscripts, including over 13,48,22,636 patients showed that the association between Semaglutide and NAION is statistically reproducible across various cohorts reporting adjusted hazard ratio (HR) ranging from 2.17 to 2.81 (Grauslund et al, Dimonsen et al.). A two-fold increased risk of NAION was observed compared to non-users or those on SGLT-2 inhibitors. However, the absolute risk remains low with an incidence rate of 0.2/1000 person-years with case reports validating NAION occurrence in patients with pre-existing anatomical risk factors or vascular comorbidities, highlighting plausible vascular or perfusion-related mechanisms.

This study suggests a possible safety signal between Semaglutide and NAION, requiring clinical awareness. Future studies integrating ophthalmic assessments, dose-response correlations are essential to establish causation.