Novo Nordisk reported that two large Phase III trials testing oral semaglutide in early Alzheimer’s disease did not slow clinical decline, according to company statements and regulatory disclosures. The trials enrolled more than 3,800 patients with confirmed amyloid pathology and compared Rybelsus (oral semaglutide) with placebo on standard-of-care background therapy. The topline readouts showed no improvement on the primary cognitive-functional endpoint (Clinical Dementia Rating–sum of boxes). Novo’s shares fell sharply on the announcement, reflecting investor concern about the program and the broader question of whether GLP-1 receptor agonists can affect neurodegeneration. The negative result contrasts with ongoing interest in incretin biology for neurodegenerative diseases and will force sponsors and investors to reassess Alzheimer’s indications for metabolic drugs. Regulators and trialists will scrutinize trial design and biomarker readouts as the field digests the data.