After weight loss, heart disease, and liver disease, can semaglutide also "fight dementia"? Novo Nordisk "places great hope" on it.

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Since the launch of semaglutide seven years ago, the application of Novo Nordisk's GLP-1 drug has expanded from obesity and diabetes to heart and liver diseases. At present, Novo Nordisk is testing its efficacy for Alzheimer's disease.

This fall, Novo Nordisk will announce the clinical trial results of its GLP-1 drug semaglutide for the treatment of Alzheimer's disease. If the trial is successful, GLP-1 drugs could completely change the way Alzheimer's disease is treated.

This research originated from an unexpected discovery in Danish health registry data. Diabetic patients using Novo Nordisk’s previous generation GLP-1 drug Victoza or similar medications had about a 20% lower risk of dementia compared to other treatments. This finding prompted Novo Nordisk to launch a large-scale clinical trial targeting Alzheimer's disease.

UBS analysts estimate that Novo Nordisk’s probability of success in the Alzheimer's disease treatment field is only one in ten, but if successful, the company could gain an additional $15 billion in annual sales revenue. Novo Nordisk's Chief Scientific Officer Martin Holst Lange said:

We are excited about this, but also see it as a very, very high-risk project.

For Novo Nordisk, which is under pressure from slowing growth, the success or failure of this investment is crucial. This year, the company has lowered its growth expectations twice, having to address competition from compounding pharmacies selling cheaper similar drugs as well as the launch of more potent GLP-1 products by Eli Lilly.

Novo Nordisk’s stock price has fallen by more than 58% in the past 12 months, far exceeding Eli Lilly’s 23% drop. However, analysts believe that even if Novo Nordisk's research fails, academic research into GLP-1 drugs for Alzheimer's disease will continue.

(Novo Nordisk’s US stock price fell more than 58% in the past 12 months)

Treatment Mechanism Overturns Traditional Thinking

Currently approved Alzheimer's disease drugs mainly work by targeting amyloid protein, a toxic misfolded protein that accumulates in the brains of Alzheimer's patients.

The therapeutic approach of semaglutide is entirely different; it mimics a gut hormone called GLP-1, and researchers believe the drug may work by reducing inflammation and altering the way the brain metabolizes glucose.

Multiple studies show that diabetic patients are more prone to dementia, providing reasonable evidence of a link between the two. Howard Fillit, co-founder and chief scientific officer of the Alzheimer's Drug Discovery Foundation, said that if successful, semaglutide would "become one of the first anti-aging drugs."

Michal Schnaider Beeri, director of the Alzheimer’s Disease Research Center at Rutgers University, said:

If they can prove something, it would be amazing. I’m very hopeful.

Trial Design Faces Practical Challenges

Despite the promising outlook, Alzheimer's disease is a recognized “forbidden zone” in drug R&D, where hundreds of promising studies have ultimately ended in failure.

The design of this trial itself also has challenges. Jared Holz, healthcare strategist at Mizuho Securities, pointed out that conducting preventive trials in healthy volunteers is “very costly and operationally complicated.”

Therefore, Novo Nordisk chose to test the drug’s ability to slow disease progression in patients with mild symptoms who have already tested positive for amyloid in the brain. Holz added:

A major challenge for many clinical trials in Alzheimer’s disease is that when treatment starts, the patient’s condition may have already progressed to a relatively advanced stage.

However, he added that even if the study shows only a slight benefit, some people might start taking semaglutide as a preventive measure.

Currently approved Alzheimer’s drugs, such as those from Eisai and Eli Lilly, mainly slow disease progression by clearing toxic β-amyloid plaques from the brain, but with limited effect and serious risks such as brain bleeding.

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