Background Risk of non-arteritic anterior ischaemic optic neuropathy (NAION) following exposure to glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes and/or obesity remains unclear. The aim of this study was to investigate NAION incidence across randomised placebo-controlled trials evaluating the GLP-1RAs liraglutide and semaglutide. Methods Pooled safety evaluation of NAION incidence from completed phase II, III and IV randomised placebo-controlled trials that evaluated the six Novo Nordisk-manufactured GLP-1RA products (active ingredients: liraglutide and semaglutide) in people with type 2 diabetes and/or overweight/obesity. Potential NAION cases were identified and categorised based on the likelihood of NAION occurrence (definite, probable, unlikely or not assessable). Definite or probable NAION cases were considered confirmed. Results This pooled analysis included 96 829 participants (GLP-1RA-treated: n=64 917; placebo-treated: n=31 912) with 205 777 participant-years of observation (PYO) (GLP-1RA-treated: 119 393 PYO; placebo-treated: 86 384 PYO). Across all trials, three confirmed NAION cases were identified in three GLP-1RA-treated participants and five confirmed cases were identified in four placebo-treated participants. In GLP-1RA-treated participants, the incidence of confirmed NAION cases was approximately three cases per 100 000 PYO, while in placebo-treated participants, the incidence was approximately six cases per 100 000 PYO. All ophthalmologist-confirmed cases reported one or more associated risk factors (eg, age >50 years, obesity, smoking, dyslipidaemia, hypertension). Conclusion Data from randomised placebo-controlled trials with semaglutide and liraglutide do not show an increased incidence of NAION in participants receiving GLP-1RA treatment versus those receiving placebo and, thus, do not suggest a relationship between GLP-1RA use and NAION. Summary Based on data from randomised placebo-controlled trials, exposure to the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and liraglutide was not associated with an increased incidence of non-arteritic anterior ischaemic optic neuropathy (NAION) relative to placebo.