Novo Nordisk A/S Phase 3 Trials of Evoke Show No Significant Results

On November 24, 2025, Novo Nordisk A/S released the findings from its phase 3 trials, dubbed Evoke and Evoke+, which evaluated the efficacy of oral semaglutide in treating early-stage Alzheimer’s disease. The two studies involved 3,808 adults with mild cognitive impairment or mild dementia, aimed at assessing the treatment’s impact compared to a placebo.

Background of the Trials

The Evoke and Evoke+ trials are randomized, double-blind studies targeting the disease-modifying potential of semaglutide for Alzheimer’s patients. They were initiated based on a combination of real-world evidence and previous research from diabetes and obesity studies, reflecting an ongoing search for effective Alzheimer’s treatments.

Key Findings

• Semaglutide did not demonstrate a significant reduction in the progression of Alzheimer’s, measured by the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score.
• While treatment led to observable improvements in Alzheimer’s-related biomarkers, these did not correlate with clinical benefits in slowing disease advancement.
• The trials indicated that semaglutide maintained a favorable safety profile, consistent with prior studies involving this medication.

Details of the Study Population

The participants included individuals aged 55 to 85, diagnosed with mild cognitive impairment or mild dementia, and confirmed as amyloid-positive. Each participant was randomly assigned to receive either semaglutide or a placebo for a total of 156 weeks, encompassing an initial 104-week treatment phase and a subsequent 52-week extension.

Future Plans and Presentations

Due to the ineffectiveness observed, the one-year extension phase of the trials will be discontinued. Topline results will be revealed at the upcoming Clinical Trials in Alzheimer’s Disease (CTAD) conference on December 3, 2025. Full results are slated for presentation at the Alzheimer’s and Parkinson’s Diseases Conferences (AD/PD) in March 2026.

Understanding Alzheimer’s Disease

Alzheimer’s disease accounts for 60-80% of dementia cases globally. This progressive disorder leads to cognitive decline, disrupting daily life for patients and caregivers. There is a pressing need for new therapies that effectively slow disease progression.

Clinical Dementia Rating Scale

The Clinical Dementia Rating scale (CDR) involves assessing cognition and functionality through patient and caregiver interviews. The summary score, known as CDR-SB, helps to monitor disease progression in clinical settings.

About Semaglutide and Novo Nordisk

Semaglutide is a GLP-1 receptor agonist, currently marketed for type 2 diabetes and obesity management. Novo Nordisk, established in 1923 and headquartered in Denmark, focuses on combating chronic diseases, employing approximately 78,500 individuals globally and offering products in about 170 countries.

This recent phase 3 trial emphasizes the challenges that remain in finding effective Alzheimer’s treatments, despite ongoing innovation in medical research.