Non-arteritic anterior ischaemic optic neuropathy incidence in placebo-controlled clinical trials of liraglutide or semaglutide.

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.