Timing and Duration of Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy

Abstract 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 utilised Danish health registries (1996–2023). Among 201,776 metformin-treated adults initiating second-line antihyperglycaemic therapy, 123 incident NAION cases were matched to 4,920 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 socioeconomic factors, hypertension, hypercholesterolaemia, sleep apnoea, and diabetes duration. Results GLP-1RA use occurred in 63/123 cases (51.2%) and 1,688/4,920 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.