Oral semaglutide fails to slow Alzheimer’s in pair of clinical trials
Developer Novo Nordisk halts plans for one-year extension periods
Semaglutide, an anti-diabetic medication, did not slow Alzheimer’s disease progression in two large, placebo-controlled Phase 3 clinical trials sponsored by its developer, Novo Nordisk. As a result, the planned one-year extension period for both will be stopped.
The EVOKE (NCT04777396) and EVOKE+ (NCT04777409) clinical trials tested whether 14 mg of oral semaglutide, given once daily over two years, could slow Alzheimer’s when added to standard care in a total of 3,808 adults with early-stage disease.
“We sincerely thank all participants and their caregivers for their meaningful contributions,” Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, said in a company press release.
Despite the result, data from the trials is still important, according to the Alzheimer’s Association.
“While these results are not what we had hoped for, they will contribute to our understanding of this devastating and fatal disease,” Joanne Pike, PhD, Alzheimer’s Association president and CEO, said in an association press release. “The data from every clinical trial, regardless of outcome, is vital to accelerating our understanding of this disease and helps inform the next generation of clinical trials. We remain optimistic about the future of Alzheimer’s treatment and prevention, as the scientific landscape continues to diversify and expand.”
Need remains for treatments that delay Alzheimer’s progression
Alzheimer’s is a progressive disease that slowly worsens over time as nerve cells are lost, affecting memory, reasoning, and independence. It is the leading cause of dementia. There remains a need for treatments that can delay progression and ease the burden on patients and their families.
Semaglutide is a long-acting version of GLP-1, a hormone that stimulates insulin release. Insulin helps move sugar from the blood into cells, including those in the brain. More insulin may help the brain move sugar more effectively, possibly slowing the loss of nerve cells. Semaglutide is marketed as Ozempic and Rybelsus for the treatment of type 2 diabetes, and as Wegovy for weight management.
Novo Nordisk began studying semaglutide for Alzheimer’s because earlier evidence — from real-world data, preclinical research, and post-hoc findings from clinical trials on diabetes and obesity — suggested it may have a positive effect on the brain.
“Based on the significant unmet need in Alzheimer’s disease, as well as several indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success,” Lange said.
Semaglutide did not outperform a placebo in clinical trials
The main goal of EVOKE and EVOKE+ was to see whether semaglutide could slow the progression of Alzheimer’s. This was measured through changes in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score, which tracks cognition and daily function.
In the CDR-SB scale, each of six areas of cognition and daily function is scored. Changes in the total CDR-SB score from the start of the clinical trials to almost two years after were used to assess whether semaglutide slowed the progression of Alzheimer’s.
The results showed that semaglutide did not perform better than a placebo in slowing the progression of the disease. Even though semaglutide improved some biological markers linked to Alzheimer’s, these changes did not lead to a meaningful clinical benefit. Semaglutide remained safe and well-tolerated, however.
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.
Patients were between 55 and 85 years and had mild cognitive impairment or mild dementia caused by Alzheimer’s. Side effects were consistent with those observed in many other clinical trials of semaglutide.
Although semaglutide did not help with Alzheimer’s, it continues to offer proven benefits for people with type 2 diabetes, obesity, and related health problems. The company has accumulated more than 37 million patient-years of experience with semaglutide across different populations.
“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,” Lange said.
While the planned one-year extension period for both clinical trials will be stopped, Novo Nordisk will present the first full set of results at the Clinical Trials in Alzheimer’s Disease Conference on Dec. 3, 2025, with detailed data to follow in March 2026 at the Alzheimer’s and Parkinson’s Diseases Conference.
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