Glucagon-Like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients with Type 2 Diabetes

Objective: To estimate the effect of initiating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase-4 (DPP-4) inhibitors on incident nonarteritic anterior ischemic optic neuropathy (NAION) among adults with type 2 diabetes. Research Design and Methods: This active-comparator, new-user cohort emulated a pragmatic target trial using the Clinical Practice Research Datalink in United Kingdom. Patients aged ≥18 years with a physician diagnosis of type 2 diabetes, who newly initiated a GLP-1 RA or a DPP-4 inhibitor, were included. DPP-4 inhibitors were selected as the comparator because they may be used as second-line treatment, like GLP-1 RAs, and have no established association with NAION. We estimated risks, risk differences (RDs), and risk ratios (RRs) of incident NAION adjusted using propensity score fine stratification weighting. Results: At one year, there were 14 NAION events among 106,858 GLP-1 RA initiators (18.5 per 100,000) and 53 among 416,369 DPP-4 inhibitor initiators (7.2 per 100,000): GLP-1 RAs were associated with an increased risk of NAION compared with DPP-4 inhibitors (RR: 2.56, 95% CI: 1.44-4.86; RD: 11.3 per 100,000). The risk of NAION was higher during the first six months and diminished with longer durations of use, and was higher in patients aged