Semaglutide Fails to Demonstrate Reduction in Alzheimer’s Progression Versus Placebo

The evoke and evoke+ trials failed to demonstrate semaglutide’s superiority to placebo in reducing the progression of Alzheimer’s disease, according to a statement from Novo Nordisk.1

Announced on November 24, 2025, by both Novo Nordisk and the Alzheimer’s Association, these data mark the end of the evoke and evoke+ trials, as Novo Nordisk has also decided to terminate both trials ahead of their 1-year follow-up periods.1,2

“Based on 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,” Martin Holst Lange, MD, PhD, chief scientific officer and executive vice president of research and development at Novo Nordisk. “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.”1

The evolve and evolve+ trials were both randomized, double-blinded phase 3 trials evaluating the efficacy and safety of oral semaglutide compared to placebo on top of standard care. A total of 3808 adults aged 55-85 years were included, all of whom were suffering from mild cognitive impairment, defined as Clinical Dementia Rating (CDR) global score of 0.5, or mild dementia due to Alzheimer’s disease, defined as CDR global score of 1.0, with confirmed amyloid positivity.1

CDR is a global measure of cognition and function conducted via interviews with patients and care partners. It is a commonly used staging tool for Alzheimer’s disease in research settings, measuring 6 areas covering cognition and function. Each area is scored between 0 (no dementia) and 3 (severe dementia), with a maximum score of 18. The summary score of these 6 areas has been applied to clinical trials in the past to track progression and assess severity; in evoke and evoke+, the change in CDR-Sum of Boxes (CDR-SB) for semaglutide versus placebo was measured from baseline to week 104.1

The evoke trial saw 1855 participants randomly assigned in a 1:1 ratio to either semaglutide 14 mg or placebo for 156 weeks, while the evoke+ trial saw 1953 patients randomized the same way. Both trials included a 104-week main treatment phase and a 52-week extension. The planned primary endpoint was the change in Alzheimer’s progression, as determined by the change in CDR-SB score compared to baseline. While semaglutide did improve several Alzheimer’s-related biomarkers in both trials, there was no delay in disease progression in any arm.1

Due to this failure to display efficacy, Novo Nordisk has discontinued a planned 1-year extension period in both trials. Topline results will be presented at the Clinical Trials in Alzheimer’s Disease conference on December 3, 2025, and full results at the 2026 Alzheimer’s and Parkinson’s Disease Conferences in March 2026.1

“While these results are not what we had hoped for, they will contribute to our understanding of this devastating and fatal disease,” Joanne Pike, DrPH, Alzheimer’s Association president and chief executive officer, said in a statement. “The data from every clinical trial, regardless of outcome, is vital to accelerating our understanding of this disease and helps inform the next generation of clinical trials. We remain optimistic about the future of Alzheimer’s treatment and prevention, as the scientific landscape continues to diversify and expand.”2

References

1. Novo Nordisk. Novo Nordisk A/S: Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. November 24, 2025. Accessed November 24, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916462

2. Alzheimer’s Association. Alzheimer’s Association Statement on Oral Semaglutide Phase 3 Topline Data Release. PR Newswire. November 24, 2025. Accessed November 24, 2025. https://www.prnewswire.com/news-releases/alzheimers-association-statement-on-oral-semaglutide-phase-3-topline-data-release-302624595.html