Novo Nordisk’s oral semaglutide failed to demonstrate a slowing of cognitive decline in the Evoke and Evoke+ Phase III programs, according to topline results presented at CTAD and company releases. Investigators and sponsors reported that treatment and placebo arms had virtually identical cognitive outcomes in the trials. The negative readouts prompt reassessment of GLP-1 receptor agonists as a monotherapy avenue for symptomatic disease modification in Alzheimer’s. Novo’s topline statements and independent presentations at CTAD provided the first public look at the data, showing consistent lack of efficacy despite prior mechanistic rationale and earlier signals. Researchers at CTAD discussed implications for future trials, including the potential need for combination strategies targeting multiple pathological pathways. Drug developers focusing on metabolic or neuroinflammatory mechanisms will likely recalibrate pipelines and biomarker strategies following these results.