Even before the new data were released, several scientists had expressed skepticism.
According to Medical News Today, Zaldy Tan, director of the Bernard and Maxine Platzer Lynn Family Memory and Healthy Aging Program at Cedars-Sinai Medical Center, was among those who argued that GLP-1 compounds cross the blood–brain barrier only to a limited extent, which in his view challenges the expectation of a clear clinical effect.
Other experts noted that Alzheimer’s is driven by multiple simultaneous biological processes, making it uncertain whether targeting individual mechanisms can yield reliable results.
GLP-1 therapies nevertheless attracted attention due to their established role in diabetes and weight regulation.
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For years, the link between metabolic disorders and neurodegeneration has fueled expectations that a drug developed for one disease area might have beneficial effects in another.
Study framework and terminated extension
It was against this backdrop that Novo Nordisk launched the two large Evoke trials.
A total of 3,808 participants with early symptoms of Alzheimer’s were followed over several years in a Phase 3 design typically used to evaluate both safety and clinical efficacy.
According to a press release (1), semaglutide showed no measurable slowing of disease progression compared with placebo.
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Researchers observed some biological changes, but these did not translate into improvements in participants’ functional abilities, and the trials were therefore not extended as originally planned.
Implications for the future
The results cast GLP-1 research in a new light.
Susan Kohlhaas, executive director of research and partnerships at Alzheimer’s Research UK, stated in a press release (2) that the outcome highlights the need to understand the many processes that drive the disease.
At the same time, other researchers emphasized that the field is not necessarily closed, but that future studies will need to explore different doses, related compounds, and preventive strategies.
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Sources: Medical News Today, Novo Nordisk, Press release (1), and Press release (2).
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