Novo Nordisk reported top-line results from two Phase III trials showing oral semaglutide failed to slow clinical progression in patients with early Alzheimer’s disease. The studies enrolled roughly 3,800 participants with confirmed amyloid pathology and compared Rybelsus (oral semaglutide) to placebo on standard cognitive and functional endpoints. Novo said treatment arms showed biomarker changes but no measurable clinical benefit versus placebo. The lead finding cuts short a high-profile repurposing bet by a major GLP-1 developer and will recalibrate investor and R&D expectations for incretin-based approaches in neurodegeneration. Novo framed the trials as long shots; company statements emphasized the biomarker signals and ongoing work on alternate incretin/amycretin programs. Trial investigators and outside neurologists flagged that biomarker improvements without clinical effect underscore persistent translation gaps between surrogate endpoints and patient outcomes in Alzheimer’s research.