Wegovy and Ozempic: Could the new weight-loss drug also cure dementia?

Over 55 million people worldwide have dementia. This mind-stealing condition has a huge impact on society and the economy, so scientists are working hard to find ways to treat or prevent it. One avenue being explored is the new weight loss jab, Wegovy.

While age is by far the biggest risk factor for dementia, obesity and type 2 diabetes are also major risk factors for developing the condition. This is where Wegovy and its sister drug, Ozempic, come into the picture. Wegovy and Ozempic, a drug for the treatment of type 2 diabetes, both contain the same active ingredient called semaglutide.

Semaglutide mimics the action of a hormone, GLP-1, which is normally released from the intestines after a meal. The hormone attaches itself to receptors in the pancreas that stimulate the release of insulin, which helps lower blood sugar levels.

However, these receptors are also found in the “reward centers” of the brain, including areas that control eating. Since semaglutide is able to cross the blood-brain barrier (the protective layer around the brain), it is likely to directly change brain activity to make people feel less hungry.

A Danish study that followed people with type 2 diabetes for five years found that those treated with semaglutide or liraglutide (another diabetes drug) had a lower incidence of dementia. Type 2 diabetes is most strongly associated with vascular dementia and not with Alzheimer’s disease (the most common form of dementia), so only some forms of dementia could be reduced by semaglutide.

However, two clinical trials that began in 2021 are testing whether daily oral doses of semaglutide will slow the progress of the disease in people in the early stages of Alzheimer’s. Because it takes a long time for the disease to develop, studies are expected to be completed in 2026.

Alzheimer’s disease is believed to originate in specific regions of the cerebral cortex, the region responsible for memories and spatial navigation. But receptors for GLP-1 were not detected in the cortex, making it unlikely that semaglutide directly activates memory networks. So how could the drug cure the disease?

The brains of Alzheimer’s disease patients build up sticky plaques of amyloid-beta and clumps of tau protein inside the brain cells. These are thought to impair cognition.

Here at the University of Oxford, a clinical trial is underway that will look specifically at tau levels in people who have high levels of amyloid beta but have not (yet) developed dementia. Semaglutide is hoped to reduce cortical tau levels, leading to reduced rates of cognitive decline.

Drugs recently approved in the United States for the treatment of Alzheimer’s target amyloid beta plaques. But these drugs have proven controversial, with patients requiring hour-long infusions every two to four weeks.

These types of drugs also likely target amyloid-beta around blood vessels, leading to life-threatening side effects such as brain hemorrhages. Alternative strategies are therefore desirable, and this is where semaglutide can shine.

Inflammation

The key link between semaglutide and the reduction of Alzheimer’s disease may be neuroinflammation, a state in which the brain is chronically inflamed.

Neuroinflammation damages the blood-brain barrier, which is disrupted in both Alzheimer’s disease and vascular dementia. The Oxford study looking at tau is also looking at how semaglutide affects neuroinflammation (there are suggestions that semaglutide is anti-inflammatory in people with obesity).

It also reduces neuroinflammation in the brains of mice and restores glucose transport across the blood-brain barrier (something that is disrupted in people with Alzheimer’s).

Another drug, memantine, originally developed to treat diabetes, has been repurposed to relieve the symptoms of Alzheimer’s disease, and is still prescribed for that use today. We now eagerly await the results of the next generation of diabetes and weight loss drugs to see if they can prevent or treat Alzheimer’s disease.

In the meantime, there are lifestyle changes you can make to reduce your risk of developing the condition. These include keeping active, eating a healthy diet, maintaining a healthy weight, and quitting smoking.