GLP-1 medicine and non-arteritic anterior ischemic optic neuropathy: Literature review and perspectives

GLP-1 therapeutics (defined as GLP-1 medicine hereafter), including GLP-1 receptor (GLP-1R) agonists (i.e. semaglutide) and glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor dual agonist (i.e. tirzepatide), were initially developed for diabetes treatment. Semaglutide and tirzepatide were then approved for treating obesity and body weight management. Beyond their capability in improving glucose disposal and lowering body weight, clinical trials are undertaking to assess their beneficial effect in other metabolic disorders. However, several recent retrospective studies indicated that semaglutide treatment increased the risk of non-arteritic anterior ischemic optic neuropathy (NAION). A few other studies, however, reported a lack of such association, or that the increased risk was very moderate. As an untreatable disorder, NAION mainly affects middle-aged and elderly people, associated with hyperglycemia and hyperlipidemia. Here, we highlighted additional beneficial effects of GLP-1 medicine, reviewed literature on the above association, and presented our view on future investigations. Based on literature controversy, the intrinsic limitations of retrospective studies, and the existence of neuroprotective effect of GLP-1 in neural systems, future meta-analyses are essential to quantitatively determine the potential association. Animal models may be utilized to explore the underlying mechanisms, if the association indeed exists. • GLP-1 medicine show beneficial effects beyond glucose homeostasis. • Increased risk on NAION with GLP-1 medicine remains controversial to date. • Benefits vs deleterious effects of GLP-1 in ophthalmic system needs further studies.