Novo Nordisk’s Phase 3 Evoke Trials Show Oral Semaglutide Does Not Slow Alzheimer’s Progression

Novo Nordisk has released topline findings from its two-year primary analysis of the phase 3 evoke and evoke+ trials, which investigated oral semaglutide in adults with early-stage symptomatic Alzheimer’s disease. The randomized, double-blind studies enrolled 3,808 participants and were designed to test whether semaglutide could slow disease progression when added to standard of care. The program was initiated based on encouraging signals from real-world data, preclinical research, and post-hoc analyses from earlier studies on diabetes and obesity.

“Based on the significant unmet need in Alzheimer’s disease as well as a number of indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success. We are proud to have conducted two well-controlled phase 3 trials in Alzheimer’s disease that meet the highest standards of research and rigorous methodology,” said Martin Holst Lange, chief scientific officer and executive vice president of Research and Development at Novo Nordisk. “We sincerely thank all participants and their caregivers for their meaningful contributions. While semaglutide did not demonstrate efficacy in slowing the progression of Alzheimer’s disease, the extensive body of evidence supporting semaglutide continues to provide benefits for individuals with type 2 diabetes, obesity, and related comorbidities.”

The results showed that semaglutide did not demonstrate superiority over placebo in slowing cognitive and functional decline, as measured by changes in the Clinical Dementia Rating–Sum of Boxes (CDR-SB) score. Although the drug produced improvements in several Alzheimer’s-related biomarkers, these biological effects did not meaningfully translate into clinical benefit regarding disease progression.

Despite the lack of efficacy in the primary endpoint, semaglutide continued to show a safety and tolerability profile consistent with previous trials, including in participants aged 55–85 with mild cognitive impairment or mild dementia due to Alzheimer’s disease. Given the results, Novo Nordisk will discontinue the one-year extension phase of the trials. The company plans to present topline findings at CTAD 2025 and share detailed data at the AD/PD 2026 conference.