Novo Nordisk says oral semaglutide failed to slow Alzheimer's in two phase 3 trials

Novo Nordisk said on November 24, 2025 that oral semaglutide did not slow Alzheimer's disease in two large phase 3 trials called EVOKE and EVOKE+, which together enrolled 3,808 adults with early symptoms ^[1]. The drug was not better than placebo on the main measure of disease progression, and Novo said the planned one-year extension of both trials will be discontinued ^[1].

Both trials were randomized, double-blind and placebo-controlled. They tested once-daily oral semaglutide 14 mg against placebo, on top of standard care, in people aged 55 to 85 with mild cognitive impairment or mild dementia due to Alzheimer's disease and confirmed amyloid positivity ^[1]. EVOKE enrolled 1,855 people and EVOKE+ enrolled 1,953, assigned 1:1 to semaglutide or placebo for a planned 156 weeks — a 104-week main treatment phase plus a 52-week extension ^[1].

The main measure was the change in the Clinical Dementia Rating–Sum of Boxes (CDR-SB) score from the start of the study to week 104 ^[1]. That scale rates six areas of cognition and function from 0 (no dementia) to 3 (severe dementia), for a top score of 18, and is used in Alzheimer's trials to track progression and severity ^[1]. Reuters reported the trials aimed for a 20% slowing of cognitive decline ^[4].

Treatment improved Alzheimer's-related biomarkers in both trials, but Novo said that "did not translate into a delay of disease progression" ^[1]. The company did not say which biomarkers changed ^[4]. Semaglutide appeared safe and well tolerated, consistent with earlier semaglutide trials, and Novo said more than 37 million patient-years of semaglutide exposure have occurred across patient populations ^[1].

Novo CEO Mike Doustdar said in a video posted on LinkedIn, "Today we announced that our efforts to slow down the progression of Alzheimer's disease have come to an end" ^[4]. Martin Holst Lange, Novo's chief scientific officer, said in the company's announcement, "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" ^[1].

The Alzheimer's Association said it was disappointed. "Though this semaglutide pill did not help against Alzheimer's, the field will continue to investigate this class of drugs, as they may act differently," said Maria C. Carrillo, the group's chief science officer ^[2]. In the United States, Leqembi and Kisunla are the only treatments approved to slow Alzheimer's progression; both are given by infusion or injection and can cause significant side effects ^[4]. Alzheimer's disease and other dementias affect more than 55 million people worldwide, and there is no cure ^[4]. The Alzheimer's Association counts 182 active clinical trials testing 138 experimental drugs ^[2].

Why it matters for patients

Nothing changes about how semaglutide is used for diabetes or weight management. It is sold as Ozempic and Rybelsus for type 2 diabetes and Wegovy for chronic weight management ^[1]. The dose tested here was once-daily oral semaglutide 14 mg — Rybelsus, a pill approved only for type 2 diabetes ^[4] — used as an experimental Alzheimer's treatment, not as a diabetes or weight drug.

The results are not evidence that semaglutide protects memory or thinking in people who take it for diabetes or weight management. The trials tested whether the drug could slow disease in people who already had mild cognitive impairment or mild dementia, so they did not test whether it can prevent Alzheimer's ^[1].

For families dealing with early Alzheimer's, the results close off one possible future option without changing what is already available. The Alzheimer's Association said approved treatments exist for people with early Alzheimer's, that patients can talk to their doctor about those options and about joining a clinical trial, and it pointed to its TrialMatch service ^[2]. Howard Fillit of the Alzheimer's Drug Discovery Foundation said in a statement that existing anti-amyloid drugs slow cognitive decline by about 30%, and that "therapies aimed at other pathways will be crucial as we chip away at the remaining 70%" ^[6].

What happens next

Topline results will be presented at the Clinical Trials in Alzheimer's Disease (CTAD) conference on December 3, 2025, and full results at the Alzheimer's and Parkinson's Diseases Conferences (AD/PD) in March 2026, according to Novo ^[1]. The CTAD meeting runs from December 1 to 4 ^[3]. Whether semaglutide will be studied again in Alzheimer's disease, alone or in combination with other drugs, has not been announced ^[4].