Data presented at the Clinical Trials on Alzheimer’s Disease (CTAD) 2025 meeting confirmed that oral semaglutide did not slow cognitive decline in the Evoke and Evoke+ phase III trials, reversing earlier hopes from preliminary signals. Novo Nordisk’s GLP‑1 candidate produced cognitive changes indistinguishable from placebo, according to the trial presentations and STAT reporting. Investigators and company representatives reviewed the full datasets at CTAD and explored potential explanations for the negative outcome, including clinical execution and mechanistic differences between trial populations and prior signals. The presentation highlighted that placebo arms performed as expected, suggesting the trials were conducted appropriately despite the negative results. The readouts close a high-profile avenue for repurposing GLP‑1 agonists in Alzheimer’s disease and will prompt companies and investigators to reassess trial designs for metabolic agents targeting neurodegeneration.