Evoke Trials Show No Alzheimer Reduction Among Semaglutide Users

Novo Nordisk’s evoke and evoke+ phase 3 trials failed to confirm oral semaglutide as superior to placebo in treating the progression of early-stage symptomatic Alzheimer disease, according to a news release.¹

“Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer’s disease, including neuroinflammation, represent potentially important and novel approaches,” wrote authors of the evoke trial findings published in Alzheimer’s Research & Therapy.² “Semaglutide may have a disease-modifying, neuroprotective effect in Alzheimer’s disease through multimodal mechanisms including neuroinflammatory, vascular, and other Alzheimer’s disease-related processes.”

The evoke (NCT04777396) and evoke+ (NCT04777409) phase 3 trials were conducted from 2021 to 2023 and explored the efficacy and safety of oral semaglutide for reducing Alzheimer disease progression. The trials’ main purposes were to further evaluate semaglutide’s impact on disease progression because of its promise across real-world studies, preclinical models, and diabetes and obesity trials.^1,2

READ MORE: New Data Show Semaglutide’s Liver Benefits Not Exclusively Tied to Weight Loss

According to the Alzheimer’s Association, recent study data show that glucagon-like peptide-1 (GLP-1) medications like semaglutide for diabetes and weight loss have potential in treating Alzheimer. GLP-1s have shown promise in reducing brain inflammation, improving blood vessel health, and providing greater protection of brain neurons.³

With these preclinical data showing promise among GLP-1s in treating Alzheimer’s, many experts expressed significant excitement and anticipation for results of the evoke trials. However, as Novo Nordisk just announced, those results were not what the pharmacy and neurological care communities had hoped for.

“The evoke and evoke+ trials did not confirm superiority of semaglutide versus placebo in the reduction of progression of Alzheimer’s disease, as measured by the change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) score compared to baseline,” wrote the authors of the news release.¹ “While treatment with semaglutide resulted in improvement of Alzheimer disease-related biomarkers in both trials, this did not translate into a delay of disease progression.”

Each evoke trial included a total of 3808 adult patients 55 to 85 years old who were experiencing mild cognitive impairment or mild dementia due to Alzheimer disease. The trials were both randomized, double-blinded, and placebo-controlled.

Semaglutide’s overall safety profile in the evoke trials demonstrated considerable success, similar to that of previous trials evaluating semaglutide for other indications. However, these results were expected, and the drug’s efficacy profile is what was most anticipated by researchers, patients, and more.

“Based on the significant unmet need in Alzheimer 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,” Martin Holst Lange, MD, PhD, chief scientific officer and executive vice president of research and development at Novo Nordisk, said in a news release.¹ “We are proud to have conducted 2 well-controlled phase 3 trials in Alzheimer’s disease that meet the highest standards of research and rigorous methodology.”

Following the 2-year evoke trial periods and the undesired trial outcomes that came from them, Novo Nordisk has made the decision to discontinue the trials’ 1-year extension period.

Despite these results, the manufacturer was grateful for its opportunity to explore such a novel approach in using a GLP-1 drug, which continues to make waves in the pharmaceutical industry. While semaglutide may be ceased in its use for Alzheimer disease, Novo Nordisk will continue to develop the drug in spaces related to diabetes, obesity, and other conditions.

“We sincerely thank all participants and their caregivers for their meaningful contributions,” concluded Lange, according to the release.¹ “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.”

READ MORE: Oral Semaglutide Shows Improvements in Blood Glucose, Cardiovascular Risk Factors

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REFERENCES

1. Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer's disease progression. News Release. Novo Nordisk A/S. November 24, 2025. Accessed November 24, 2025. https://www.globenewswire.com/news-release/2025/11/24/3193328/0/en/Novo-Nordisk-A-S-Evoke-phase-3-trials-did-not-demonstrate-a-statistically-significant-reduction-in-Alzheimer-s-disease-progression.html

2. Cummings JL, Atri A, Feldman HH, et al. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease. Alzheimers Res Ther. 2025 Jan 8;17(1):14. doi: 10.1186/s13195-024-01666-7.

3. GLP-1s and Alzheimer’s: what you need to know. The Alzheimer’s Association. October 15, 2025. Accessed November 24, 2025. https://www.alz.org/blog/2025/glp-1s-and-alzheimer-s-what-you-need-to-know