Novo Nordisk’s Evoke Phase 3 Trial Fails to Show Semaglutide Benefit in Alzheimer’s Disease

Novo Nordisk A/S recently announced the top-line results from its pivotal phase 3 Evoke and Evoke+ clinical trials investigating the effects of oral Semaglutide in patients with early-stage symptomatic Alzheimer’s disease. Despite high hopes, the trials did not demonstrate a statistically significant reduction in the progression of Alzheimer’s disease, marking a major disappointment for the company and the field of Alzheimer’s research.

The Evoke and Evoke+ trials, (Clinical Trial ID NCT04777396 and NCT04777409), were large-scale, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy of Semaglutide in slowing disease progression over a 104-week period. These studies enrolled adults aged 55 to 85 years with mild cognitive impairment or mild dementia due to Alzheimer’s disease, confirmed by amyloid biomarkers. The primary endpoint was the change from baseline in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score, a well-established measure of cognitive and functional decline in Alzheimer’s.

Unfortunately, the results showed that semaglutide did not meet the primary endpoint, failing to show statistically significant differences compared to placebo in slowing clinical progression as measured by the CDR-SB score. Despite some biomarker improvements suggesting potential biological activity of the drug, these did not translate into meaningful clinical benefits within the trial duration.

Safety and tolerability profiles of semaglutide in the Evoke trials were consistent with its known effects from prior use in Type-2 diabetes and obesity, with no new safety concerns emerging. 

Martin Holst Lange, Chief Scientific Officer and Executive Vice President of Research and Development at Novo Nordisk A/S, stated that despite the low likelihood of success, they felt a responsibility to explore semaglutide potential in Alzheimer’s disease due to significant unmet needs and indicative data. He expressed pride in conducting two rigorously controlled phase 3 trials that meet the highest research standards and thanked all participants and caregivers for their contributions. Lange emphasized that while semaglutide did not show efficacy in slowing Alzheimer’s progression, it continues to provide benefits for patients with type 2 diabetes, obesity, and related comorbidities.

Following the results, Novo Nordisk has decided to discontinue the planned one-year extension period of the Evoke and Evoke+ trials based on the efficacy outcomes observed in the overall study population. The topline results from these trials will be presented at the Clinical Trials in Alzheimer’s Disease (CTAD) conference on December 3, 2025, with full data expected at the 2026 Alzheimer’s and Parkinson’s Disease Conferences (AD/PD) in March 2026.