Timing and duration of glucagon‐like peptide‐1 receptor agonist use and risk of nonarteritic anterior ischaemic optic neuropathy

Purpose To investigate the association between glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use and nonarteritic anterior ischaemic optic neuropathy (NAION) in type 2 diabetes, examining treatment recency and cumulative duration. Methods This nationwide registry‐based nested case–control study utilizedz Danish health registries (1996–2023). Among 201 776 metformin‐treated adults initiating second‐line antihyperglycaemic therapy, 123 incident NAION cases were matched to 4920 controls by birth year and sex (incidence‐density sampling). Conditional logistic regression estimated adjusted hazard rate ratios (HRs) for GLP‐1RA exposure by recency (current 0–90 days; recent 91–365 days) and cumulative duration, adjusting for socio‐economic factors, hypertension, hypercholesterolaemia, sleep apnoea, and diabetes duration. Results GLP‐1RA use occurred in 63/123 cases (51.2%) and 1688/4920 controls (34.3%). Ever use was associated with a higher NAION rate than other second‐line therapies (HR 2.13, 95% CI: 1.43–3.18). Current use was associated with elevated rates (HR 2.28, 95% CI: 1.49–3.48), whereas the estimate for recent use was imprecise (HR 1.69, 95% CI: 0.88–3.25). By cumulative duration, no clear evidence of an increase was seen within 0–½ years (HR 0.80, 95% CI: 0.32–2.05), and rates were highest at ½–1 year (HR 3.63, 95% CI: 2.06–6.40) and 1–1½ years (HR 3.52, 95% CI: 1.73–7.17). Findings were consistent after HbA1c adjustment and in a new‐user analysis. Conclusion GLP‐1RA use is associated with a higher NAION rate in type 2 diabetes. This association appears time‐dependent, being most pronounced during current treatment and peaking after 6–18 months of cumulative exposure.