Norwegian patients and researchers at Akershus University Hospital and Oslo University Hospital have taken part in two large international studies that will likely disappoint many.
In the trials, semaglutide was provided as tablets to patients in the early stages of Alzheimer’s.(Stock photo: Shutterstock / NTB)
The Danish pharmaceutical company Novo Nordisk has had great success with the medicines Wegovy and Ozempic. They are used for weight loss and for treating type 2 diabetes.
Both medicines contain the active ingredient semaglutide, a substance that mimics the body's GLP-1 hormone. For weight loss it is still delivered by injection, but in this study the participants received it as a pill.
According to Science, the EVOKE and EVOKE+ studies arethe largest and longest studies to date in which researchers have examined whether a medication – widely known as an effective weight-loss drug – might also have an effect on a disease that attacks the brain.
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Novo Nordisk is behind the studies, in which around 3,800 people in the early stages of Alzheimer's were followed for two years. Participants received either a daily dose of up to 14 milligrams of semaglutide or a placebo.
"We had a responsibility to explore semaglutide's potential, despite a low likelihood of success," Novo Nordisk's research director Martin Holst Lange said in a press release.
Good results in earlier studies
Science notes that EVOKE was partly inspired by previous research suggesting that semaglutide and similar medications may prevent neurodegeneration – the gradual breakdown of nerve tissue in the brain.
Individuals taking these drugs for diabetes have shown lower rates of Parkinson’s and Alzheimer’s. A study published in the journal Alzheimer's & Dementia, for instance, found that people with type 2 diabetes using medications containing semaglutide had between 40 and 70 per cent lower risk of developing Alzheimer's disease.
Animal studies have also shown reduced inflammation in the nervous system and body, as well as slower accumulation of brain plaque, a key feature of Alzheimer’s.
But researchers involved in the EVOKE studies now believe that stopping a neurodegenerative process after it has already begun may involve something else.
"Disappointing"
Geir Selbæk is the research director at the Norwegian National Centre for Ageing and Health. He follows developments in this field closely.
"The results are disappointing. Earlier studies in certain high-risk groups hinted at a positive effect, and there are plausible explanations for how these medications might work in the brain," Selbæk tells Science Norway.
He also notes something encouraging: The treatment in the study did influence biomarkers linked to Alzheimer’s disease, though unfortunately without any observable effect on symptoms.
Biomarkers are proteins, molecules, or other substances that can be measured in the blood or bodily tissue to give doctors information about disease.
"It is still unclear whether starting treatment earlier, or focusing on subgroups with particular risk profiles, such as people with cardiovascular disease or diabetes, may have an effect," he says, adding:
"It’s crucial to investigate multiple approaches for treating dementia-related disorders, as effective therapy will likely require several lines of attack. We are eagerly awaiting a more detailed presentation of the findings."
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May have other beneficial effects
In the Norwegian part of the study, 21 patients were set to take part. Some would receive semaglutide tablets, while others would receive a placebo. Participants were to undergo clinical examinations, have blood samples taken, and be interviewed.
Daniel Drucker, a GLP-1 expert at the University of Toronto who was not involved in the research, notes – like Selbæk – that important findings may still emerge from the EVOKE results that have not yet been released.
He and other researchers are, according to Science, particularly curious as to whether analyses will show that semaglutide has anti-inflammatory effects in the brain.
The large size of the studies and the high number of participants without diabetes or obesity may also help determine whether the drug's anti-inflammatory properties are independent of weight loss, as earlier studies have suggested.
He also reminds us that, in addition to serving as a weight-loss and diabetes medication, GLP-1 drugs can reduce the risk of heart attacks, strokes, and other cardiovascular diseases. These are also drugs with few side effects.
