The truth about the semaglutide Alzheimer's trials

In 2025, Novo Nordisk announced disappointing results from its semaglutide Alzheimer's trial. But that's not the end of the story. Find out why.



The semaglutide Alzheimer's trials were dubbed 'EVOKE' and 'EVOKE+'. Both had the same goal: to find out whether semaglutide had any effect on people diagnosed with early Alzheimer's disease.⁹

To this end, researchers enrolled nearly 4,000 participants, all of whom had mild cognitive impairment or mild dementia due to Alzheimer's disease.⁹

The participants were randomly assigned to receive either:⁹

• A regular dose of oral (tablet-based) semaglutide
• A placebo – a dummy drug containing no medication
  
  

Researchers were looking for a difference between these two groups. If the semaglutide group showed more progress than the placebo group, that would suggest semaglutide had a positive effect.

Unfortunately, this wasn't to be. In November 2025, Novo Nordisk – the study's sponsor – announced it would be cutting the trials short due to a negative clinical result.⁸

It turned out that the semaglutide group had shown improvements in Alzheimer's disease-related biomarkers – telltale bodily signs of the condition. However, this didn't translate into real-world improvements for those participants.⁸

'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, despite a low likelihood of success', explained Novo Nordisk's chief scientific officer.⁸

'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.'

Why these results weren't a 'failure'

The results of the EVOKE trials were deeply disappointing – for the researchers, the participants and the countless people worldwide affected by Alzheimer's disease.

However, they weren't a 'failure' in the traditional sense, because the study did what it set out to do.

Researchers wanted to find out whether semaglutide could slow the progression of Alzheimer's. The answer, unfortunately, was 'no'. But it was an answer nonetheless.

In this sense, a clinical trial only 'fails' when it falls apart. That could be due to flawed design, poor recruitment or high dropout rates, or because its results are later discredited.

However, the EVOKE trials had all the hallmarks of well-designed, clinically sound studies. They were:⁹

• Built on solid evidence (including animal and real-world studies)
• Randomised, double-blinded and placebo-controlled – essential for ensuring an accurate, unbiased result
• Conducted across several countries with large numbers of participants, which helps smooth out statistical anomalies
  
  

So, what should we take from all this?

To put it simply, a good study is never a wasted study.

Ultimately – and despite the disappointing results – the EVOKE trials did their bit to advance research into Alzheimer's disease. They showed researchers that semaglutide probably isn't worth pursuing as a potential treatment.

Alzheimer's disease is complex, and researchers are pursuing many different avenues as they strive to find viable treatments and therapies. Negative results, such as those from the EVOKE trials, help researchers allocate budget and resources to other, potentially more fruitful avenues of research.

So, what feels like a step sideways could, at least in a small way, be a step forward.

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Sources

1. Wilding, J.P.H. et al. (2021) "Once-Weekly Semaglutide in Adults with Overweight or Obesity" The New England Journal of Medicine, 384(11) https://doi.org/10.1056/NEJMoa2032183

2. Medicines and Healthcare products Regulatory Agency (2024) "MHRA approves GLP –1 receptor agonist semaglutide to reduce risk of serious heart problems in obese or overweight adults" [press release]. GOV.UK. Retrieved from
https://www.gov.uk/government/news/mhra-approves-glp-1-receptor-agonist-semaglutide-to-reduce-risk-of-serious-heart-problems-in-obese-or-overweight-adults

3. Lincoff, A.M. (2023) "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes" The New England Journal of Medicine, 389(24) https://doi.org/10.1056/NEJMoa2307563

4. Hendershot, C.S. et al. (2025) "Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial" JAMA Psychiatry, 82(4) https://doi.org/10.1001/jamapsychiatry.2024.4789

5. O'Keefe, J.H.O. et al. (2025) "Anti-consumption agents: Tirzepatide and semaglutide for treating obesity-related diseases and addictions, and improving life expectancy" Progress in Cardiovascular Disease, 89:102–112 https://doi.org/10.1016/j.pcad.2024.12.010

6. National Library of Medicine (2026) A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE) (EVOKE). Retrieved from https://clinicaltrials.gov/study/NCT04777396

7. National Library of Medicine (2025) A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE Plus) (EVOKE Plus). Clinicaltrials.gov. Retrieved from https://clinicaltrials.gov/study/NCT04777409

8. Novo Nordisk (2025) Novo Nordisk A/S: Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer's disease progression [company announcement]. Retrieved from https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916462

9. Cummings, J.L. et al. (2026) "Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials" The Lancet https://doi.org/10.1016/S0140-6736(26)00459-9

This article was reviewed and approved by Lujain Alhassan, Bariatric Nutritionist, on 3 April 2026.