Key Highlights
- Novo Nordisk announced that phase 3 trials of semaglutide for early-stage symptomatic Alzheimer’s disease did not show a statistically significant reduction in disease progression.
- The two-year primary analysis involved 3,808 adults and evaluated the efficacy and safety of oral semaglutide compared to placebo on top of standard of care.
- While biomarker improvements were observed, they did not translate into delayed disease progression.
- No further extension period will be conducted in the evoke/evoke+ trials based on current results.
Novo Nordisk’s Semaglutide Trials for Alzheimer’s Disease Show Limited Success
Bagsværd, Denmark – In a significant update to its research and development efforts, Novo Nordisk has announced that the phase 3 trials of semaglutide in early-stage symptomatic Alzheimer’s disease did not demonstrate a statistically significant reduction in disease progression. The findings, based on a two-year primary analysis involving over 3,800 participants, underscore the complexity of developing novel treatments for this progressive neurological disorder.
Background and Research Context
The decision to investigate semaglutide’s potential in Alzheimer’s disease was driven by real-world evidence studies, preclinical models, and post-hoc analyses from diabetes and obesity trials. Semaglutide is a GLP-1 receptor agonist already approved for treating type 2 diabetes under the brand names Ozempic® and Rybelsus®, as well as for weight management with Wegovy®. Its efficacy in slowing disease progression was a key area of interest, given the significant unmet need in Alzheimer’s treatment.
Results of the Phase 3 Trials
The phase 3 trials, dubbed evoke and evoke+, were global, randomized, double-blind, placebo-controlled studies designed to assess the efficacy, safety, and tolerability of oral semaglutide at a dose of 14 mg daily compared to placebo in early-stage symptomatic Alzheimer’s disease. Patients aged between 55 and 85 years with mild cognitive impairment or mild dementia due to Alzheimer’s disease were enrolled. Despite improvements in biomarkers associated with the disease, these changes did not translate into a delay in progression as measured by the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score.
Martin Holst Lange, chief scientific officer and executive vice president of Research and Development at Novo Nordisk, expressed both pride and disappointment. “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,” he stated during a press conference. “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.”
Future Implications
In light of these results, Novo Nordisk has decided to discontinue the one-year extension period in the evoke and evoke+ trials. Topline results from both studies will be presented at the Clinical Trials in Alzheimer’s Disease (CTAD) conference on December 3, 2025, with full findings scheduled for presentation at the 2026 Alzheimer’s and Parkinson’s Diseases Conferences.
Novo Nordisk remains committed to advancing research in chronic diseases. The company continues to explore other therapeutic avenues through its robust pipeline of products and innovations aimed at improving patient outcomes.
Note: All dates, names, numbers, and quotes have been preserved exactly as stated in the original article.
