Semaglutide Fails to Slow Progression of Alzheimer Disease Compared to Placebo: Novo Nordisk Phase 3 Trial Update

Novo Nordisk's 2-year phase 3 trials testing oral semaglutide for early-stage Alzheimer disease (AD) failed to meet their primary endpoint, the company announced today. The evoke and evoke+ trials, which enrolled 3,808 adults with mild cognitive impairment or mild dementia due to AD, did not demonstrate superiority of semaglutide compared with placebo in reducing disease progression as measured by change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) score from baseline.

The global randomized, double-blind phase 3 confirmatory trials evaluated oral semaglutide 14 mg once daily compared to placebo on top of standard of care in adults aged 55 to 85 years with confirmed amyloid positivity. Novo reported that while investigators reported inprovement in AD-related biomarkers in participants treated with semaglutide in both evoke and evoke,+ the surrogate markers did not translate into delayed progression of the disease.

"We Had a Responsibility to Explore..."

The decision to pursue an indication for semaglutide in AD was based on a plethora of data accumulated from the more than 37 million patient-years of semaglutide exposure across a diverse range of populations, the company stated, from real-world evidence studies, preclinical models, and post-hoc analyses from diabetes and obesity trials.

"Based on the significant unmet need in [Alzheimer] 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," Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, said in a statement. "We are proud to have conducted 2 well-controlled phase 3 trials...that meet the highest standards of research and rigorous methodology."

Evoke enrolled 1,855 and evoke+ 1,953 participants who were randomly assigend to receive semaglutide or placebo for 156 weeks, a span that included a 104-week main treatment phase and 52-week extension, Novo Nordisk said. The company noted that it will discontinue the 1-year extension period based on the efficacy results observed in the overall study population.

Consistent with previous trials of semaglutide, the glucagon-like peptide 1 (GLP-1) receptor agonist's safety and tolerability profile was favorable, according to the company. The incretin mimetic is currently marketed as Ozempic (subcutaneous injection) and Rybelsus (oral) for type 2 diabetes and Wegovy (subcutaneous injection) for chronic weight management.

"While semaglutide did not demonstrate efficacy in slowing the progression of [Alzheimer] disease, the extensive body of evidence supporting semaglutide continues to provide benefits for individuals with type 2 diabetes, obesity, and related comorbidities," Lange said.

Data Will Be Presented

Novo Nordisk plans to present topline results from the the phase 3 trials at the Clinical Trials in Alzheimer's Disease (CTAD) conference on December 3, 2025, with full results scheduled for the Alzheimer's and Parkinson's Diseases Conferences (AD/PD) in March 2026.

References

Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer's disease progression. News release. Novo Nordisk. November 24, 2025. Accessed November 24, 2025. https://ml-eu.globenewswire.com/Resource/Download/1328a3cb-6359-4bb8-aef1-c7eab58d3016