Semaglutide for Early Alzheimer's Disease

(EVOKE Trial)

Not currently recruiting at 800 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Alzheimer's treatments

Disqualifiers: Parkinson's, Schizophrenia, Bipolar, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 17

Duration: 173 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medication semaglutide can benefit individuals with early Alzheimer's disease. Participants will receive either semaglutide (known by brand names such as Ozempic, Wegovy, and Rybelsus) or a placebo (a substance with no active medication) to compare effects. The study spans about 3 years and includes several clinic visits and tests. It seeks individuals aged 55 to 85 with mild memory problems (mild cognitive impairment or mild Alzheimer's) who must bring a study partner. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

If you are taking an approved Alzheimer's treatment, you can continue as long as your dose has been stable for at least 3 months before the trial and doesn't change during the trial unless necessary.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that semaglutide is generally safe for people. It is already used safely for conditions like type 2 diabetes, which provides some confidence about its safety in Alzheimer's trials. Common side effects include nausea and vomiting, but these are usually manageable.

Other studies have not raised any major safety concerns with semaglutide. In fact, some studies have linked it to a lower risk of developing Alzheimer's in diabetes patients. This suggests it might be safe for people with early Alzheimer's as well. However, it is important to remember that every treatment carries some risks, and side effects can vary from person to person. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about semaglutide for early Alzheimer's disease because it offers a novel approach compared to current treatments like cholinesterase inhibitors and memantine. Unlike these standard treatments, semaglutide is originally used for diabetes management and works by mimicking a hormone called GLP-1, which can help in reducing inflammation and possibly protecting brain cells. Additionally, semaglutide is taken orally once daily, which might provide a convenient option for patients. This unique mechanism and delivery method have sparked interest as they could lead to improved outcomes for those with early Alzheimer's disease.

What evidence suggests that semaglutide might be an effective treatment for early Alzheimer's disease?

Research has shown that semaglutide, a type of medication, might help slow Alzheimer's disease. In earlier studies, people with type 2 diabetes who took semaglutide experienced 40%-70% fewer Alzheimer's-related problems, suggesting that semaglutide might protect the brain. This trial will compare oral semaglutide with a placebo to evaluate its effectiveness in early Alzheimer's disease. The drug affects several pathways related to the disease, potentially slowing its progression. Early trials have shown positive results for semaglutide, indicating promise for treating early Alzheimer's disease. ^{3 4 5 6 7}

Who Is on the Research Team?

Clinical Transparency (Dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

The EVOKE trial is for people aged 55-85 with early Alzheimer's, having an MMSE score of ≥22 and specific memory index scores. They must have stable Alzheimer's medication for 3 months if applicable, and show amyloid presence via PET or CSF tests. A study partner is required. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

My tests show amyloid buildup in my brain.

You scored 22 or higher on the Mini-Mental State Examination.

My Alzheimer's medication dose has been stable for 3 months.

Exclusion Criteria

A brain scan shows signs of specific types of strokes confirmed by a specialist.

I have a neurological disorder that is not mild cognitive impairment or mild Alzheimer's.

You have a serious mental health condition that is not stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or placebo for up to 173 weeks

173 weeks

17 clinic visits, 1 phone call

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension Phase

Participants continue to be monitored for changes in cognitive and functional scores

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo (semaglutide)
• Semaglutide

Trial Overview Semaglutide's effect on early Alzheimer’s disease is being tested against a placebo over approximately 3 years with clinic visits and one phone call. Participants will undergo various tests, scans, and blood samples to assess the medicine's impact.

How Is the Trial Designed?

Group I: Oral Semaglutide Experimental Treatment 1 Intervention

Participants are given oral semaglutide once daily

Group II: Placebo (semagludtide) Placebo Group 1 Intervention

Participants are given oral placebo once daily

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Memantine, a drug that blocks NMDA receptors, showed a small but significant benefit in patients with moderate-to-severe Alzheimer's disease after 28 weeks, with a mean difference of 0.3 in the global score compared to placebo.

Patients taking memantine experienced less deterioration in daily living activities, with a score change of 2.1 compared to 3.4 in the placebo group, highlighting its potential as a valuable treatment option in a field with limited effective medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is memantine a breakthrough in the treatment of moderate-to-severe Alzheimer's disease? Doggrell, S.[2019]

Current Alzheimer's disease treatments mainly focus on improving symptoms rather than halting disease progression, with only selegiline and vitamin E showing any delay in important clinical endpoints.

Research is ongoing for new treatments aimed at slowing progression or preventing onset, including antioxidants, anti-inflammatory agents, and drugs targeting amyloid deposition, with trials also focusing on preventing Alzheimer's in individuals with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials to slow progression and prevent disease onset. Thal, LJ.[2019]

Selegiline showed a statistically significant but clinically unimportant improvement in cognitive performance and activities of daily living in Alzheimer's patients during the short term (4-17 weeks), based on data from 821 patients across 14 trials.

No long-term benefits were observed, and there were no significant differences in emotional state or overall global response between selegiline and placebo, indicating limited efficacy for this treatment in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials. Wilcock, GK., Birks, J., Whitehead, A., et al.[2019]

Citations

1. alz.org alz.org/blog/2025/glp-1s-and-alzheimer-s-what-you-need-to-know

GLP-1s and Alzheimer's: What You Need to Know While semaglutide is the first GLP-1 being studied in large Alzheimer's trials, it is not the only drug of interest. Other GLP-1s may also have ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12262134/

Associations of semaglutide with Alzheimer's disease-related ... In a recent real-world emulation trial in T2D patients, we showed that semaglutide was associated with a significant 40%-70% reduction in AD ...

3. brightfocus.org brightfocus.org/resource/how-glp-1s-could-transform-alzheimers-treatment/

How GLP-1s Could Transform Alzheimer's Treatment Glucagon-like peptide-1 (GLP-1) drugs, like Ozempic® and Wegovy®, may slow Alzheimer's progression. · They target multiple disease pathways at ...

4. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-024-01666-7

evoke and evoke+: design of two large-scale, double-blind ... Treatment with GLP-1RAs significantly decreases risk of dementia, and in preclinical studies, the GLP-1RA semaglutide has shown positive effects ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12056300/

A pooled analysis of semaglutide in adults aged ≥ 65 years The evoke and evoke+ trials are investigating the efficacy and safety of semaglutide in participants aged 55 to 85 years with early Alzheimer's ...

6. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14313

Associations of semaglutide with first‐time diagnosis of ... Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39445596/

Associations of semaglutide with first-time diagnosis ... - PubMed Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications.