Losing the Gamble on Semaglutide in Alzheimer’s Disease

Novo Nordisk made a bold gamble on oral semaglutide for delaying the progression of Alzheimer’s disease. Yesterday, as can happen with bold gambles, it did not pay off. A daily 14 mg oral dose of semaglutide was no better than placebo for preventing disease progression as measured by the Clinical Dementia Rating – Sum of Boxes score.

This was a costly gamble. Novo Nordisk paid for two randomized controlled trials with a total of 3,808 patients studied for two years. The cost of just one of these trials can easily total hundreds of millions of dollars. And then, there is the cost of the hit to the stock price. After Novo Nordisk announced this disappointing news, the value of Novo Nordisk stock dropped by 5.6%. That’s about seven billion dollars of value erased from the value of the company according to the stock market.

Ouch.

Low Likelihood of Success

Novo’s chief scientific officer and VP of R&D explained that the company took this risk knowingly:

“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. We are proud to have conducted two well-controlled phase 3 trials in Alzheimer’s disease that meet the highest standards of research and rigorous methodology.”

Making it clear that they knew this was risky, the company had described these two studies as a “lottery ticket.” This is a reminder that lottery tickets often turn out to be worthless.

A Caution About Observational Signals

An important lesson in all of this is that observational findings that signal the possibility of an effect sometimes turn out to be false signals. Novo spent all this money based on data from post-hoc analyses, real-world observational studies, and pre-clinical models. All of it was valid research – but not evidence for effectiveness.

For that, you need a randomized controlled trial. Novo now has two of them and they cost the company billions of dollars in the end. Bold gambles do not always pay out.

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A Game of Tric Trac, painting by Judith Leyster / WikiArt

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November 25, 2025