Novo Nordisk reported that two large Phase III trials testing oral semaglutide (Rybelsus) failed to slow cognitive decline in patients with early symptomatic Alzheimer’s disease and confirmed amyloid pathology. The company released top-line results showing no effect on the primary cognitive and functional endpoint across 3,808 participants. The trials, dubbed Evoke and Evoke+, were among the highest-profile tests of GLP-1 receptor agonists in neurodegeneration. Novo Nordisk led the studies and will publish detailed data and analyses to explain subgroup performance, dosing, and secondary endpoints. The failure undercuts the hypothesis that systemic GLP-1 agonism can modify Alzheimer’s progression and will likely force sponsors and investors to reassess GLP-1 repurposing strategies. Regulators and trialists will watch the full dataset to see whether any signal emerged on biomarkers or specific patient subsets.