Novo Nordisk has reported top-line findings from its two major phase 3 Alzheimer’s disease trials, evoke and evoke+, revealing that oral semaglutide did not demonstrate superiority to placebo in slowing disease progression in patients with early-stage symptomatic Alzheimer’s disease. The results mark a disappointing outcome for one of the world’s most widely used metabolic therapies, tested in a new neurological indication amid rising scientific interest in the potential cognitive benefits of GLP-1 medicines.
The evoke and evoke+ trials were robustly designed, randomized, and double-blinded, enrolling a combined 3,808 adults between the ages of 55 and 85. All participants had been diagnosed with mild cognitive impairment or mild dementia caused by Alzheimer’s disease and received either semaglutide or placebo in addition to standard of care. The trials were conducted over two years, forming the primary analysis window for evaluating the treatment’s effectiveness.
Novo Nordisk initiated the Alzheimer’s disease program based on a growing body of real-world evidence, supportive mechanistic models, and post-hoc analyses from large diabetes and obesity studies. These earlier findings had suggested that GLP-1 receptor agonists like semaglutide might influence neuroinflammation, amyloid pathways, or metabolic processes linked to neurodegeneration.
However, the phase 3 data did not confirm a clinical benefit. According to the company, semaglutide failed to demonstrate superiority over placebo when measured by the change from baseline in the Clinical Dementia Rating–Sum of Boxes (CDR-SB), the gold-standard endpoint for determining progression in early Alzheimer’s disease. While semaglutide did improve several Alzheimer’s-related biomarkers across both trials, these biological changes did not translate into measurable cognitive or functional slowing of the disease.
Safety findings may offer some reassurance to clinicians and patients. Semaglutide’s safety and tolerability profile in the evoke trials appeared consistent with results from prior studies in diabetes and obesity, with no unexpected adverse events observed. Novo Nordisk noted that the therapy has now accumulated more than 37 million patient-years of exposure across diverse global populations, reinforcing its strong safety track record in approved indications.
Martin Holst Lange, Novo Nordisk’s chief scientific officer and executive vice president of Research and Development, acknowledged both the high hopes and challenges of pursuing an Alzheimer’s indication.
“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,” he said. “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.”
Following the results, Novo Nordisk confirmed that the planned one-year extension period for both evoke trials will be discontinued. The company will present full topline findings at the Clinical Trials in Alzheimer’s Disease (CTAD) conference on 3 December 2025, with comprehensive data expected at the 2026 Alzheimer’s and Parkinson’s Diseases Conference (AD/PD) in March 2026.
Although the outcomes mark a setback for semaglutide in neurology, the trials add to the broader scientific understanding of metabolic pathways in Alzheimer’s disease, and Novo Nordisk emphasized that it remains committed to advancing research across multiple therapeutic areas.