Novo Nordisk has announced that its two Phase 3 trials of an oral form of semaglutide failed to slow the progression of Alzheimer’s disease, ending hopes that the widely used weight-loss and diabetes drug could be repurposed for neurodegenerative conditions.
The EVOKE and EVOKE+ trials involved more than 3,800 participants aged 55 to 85 who were diagnosed with early-stage Alzheimer’s, including those with mild cognitive impairment and mild dementia.
The primary endpoint of the trials was the change in Clinical Dementia Rating – Sum of Boxes (CDR‑SB) over 104 weeks. While semaglutide showed some improvements in Alzheimer’s-related biomarkers, these did not translate into measurable differences in cognitive function or daily functioning compared with placebo. Due to the lack of clinical benefit, Novo Nordisk has discontinued the planned one-year extension of the studies.
The trials confirmed that semaglutide was well tolerated, with a safety profile consistent with its previous use in diabetes and obesity. Despite the negative outcome for Alzheimer’s, the drug continues to provide significant benefits for its approved indications. Researchers and organizations, including the Alzheimer’s Association, noted that the trial data will still contribute valuable information to ongoing efforts to understand the disease and develop effective treatments.
Novo Nordisk plans to present detailed data from the trials at the Clinical Trials in Alzheimer’s Disease (CTAD) conference in December 2025, with additional full results expected at the 2026 Alzheimer’s & Parkinson’s Diseases Conference.
The outcome highlights the challenges of repurposing existing metabolic drugs for neurodegenerative diseases, while underscoring the continued need for innovative approaches to treat Alzheimer’s, which affects millions of people worldwide.
