A small clinical trial suggests that drugs like Ozempic could potentially be used not just for diabetes and weight loss but to protect the brain, slowing the rate at which people with Alzheimer’s disease lose their ability to think clearly, remember things and perform daily activities. The results need to be borne out in larger trials, which are already underway, before the medicines could receive approval for the disease.
The study, of 204 people with Alzheimer’s disease in the United Kingdom, found that those taking the diabetes drug liraglutide – an earlier medication in Ozempic’s class, which are known as GLP-1 receptor agonists – had 18% slower cognitive decline over the course of a year compared with those taking a placebo.
The trial’s main goal, though – changing the rate at which the brain metabolizes glucose – was not met, which researchers suggested could have been a result of its small size. The findings were shared Tuesday at the Alzheimer’s Association International Conference in Philadelphia and haven’t yet been published in a peer-reviewed journal.
“We’ve known for some time through animal work that GLP-1 has a different type of activity in the brain,” said Dr. Maria Carrillo, chief science officer and medical affairs lead for the Alzheimer’s Association, which was not involved with the research. “This study really demonstrates for us the possibilities that are there.”
Beyond diabetes and weight loss
GLP-1 drugs have exploded in use in recent years for diabetes and weight loss, and they have shown benefits for a wide range of other health conditions, such as protecting the heart and kidneys, reducing sleep apnea and potentially helping with addiction.
Studies in animals have suggested that in the brain, the medicines can reduce neuro-inflammation, tamp down on toxic proteins known as amyloid and tau, improve insulin resistance and increase synaptic function, or the transmission of impulses between cells, said Dr. Paul Edison, professor of neuroscience at Imperial College London, who led the trial.
“This is the first study that actually looked at a relatively large number of patients for whether there is any neuroprotective effect in Alzheimer’s disease,” Edison said.
The trial enrolled predominantly people with mild Alzheimer’s disease, measured by a test known as the Mini-Mental State Examination, a scale that goes up to 30. Those with a score of 21 to 26 are considered to have mild Alzheimer’s disease, and the majority of participants in this study had a score of about 22, although some had scores down to 17, indicating moderate Alzheimer’s, Edison said.
It excluded patients with diabetes to try to control for any effects of that disease, which is itself a risk factor for Alzheimer’s.
Edison and his team ran the trial using liraglutide, a daily injection sold under the brand names Victoza for diabetes and Saxenda for weight loss, because it’s similar to the GLP-1 hormone found in humans, he said, and it was on the market for diabetes when the study started about a decade ago.
Ozempic, which uses the active ingredient semaglutide, was approved in the US for diabetes in 2017 and subsequently in the UK, and its counterpart for weight loss, Wegovy, was approved in the US in 2021. They are given as injections once a week.
The GLP-1 drug class also includes Eli Lilly’s Mounjaro and Zepbound, which use the active ingredient tirzepatide, which mimics not just the hormone GLP-1 but another called GIP. And a snowballing number of additional companies are trying to develop even more powerful drugs. Already, the existing medicines are in shortage as the companies try to keep up with soaring demand.
Competing in Alzheimer’s
Lilly already has a business in Alzheimer’s, gaining approval this month of a treatment called Kisunla that clears buildups of amyloid plaques from the brain. But it hasn’t announced any trials of its GLP-1 drugs in Alzheimer’s.
“So I would just caution,” he continued, “that this is probably the most risky trial that we have ever undertaken.”
Novo Nordisk is running its trials using a daily pill form of semaglutide, with results expected as soon as the fall of 2025. An oral form is already on the market for diabetes under the brand name Rybelsus.
When it announced the studies in 2020, the Danish drug giant said it planned to enroll about 3,700 people with early Alzheimer’s disease, with a main treatment period of about two years.
The company said in a later investor presentation that its decision to start the phase three trials was based on data including real-world evidence studies showing lower risks of dementia among people on GLP-1 medicines, analyses of effects seen in other clinical trials and animal studies showing that the drugs are associated with improved memory function, reduced neuroinflammation and systemic anti-inflammatory effects.
Earlier this month, a review by researchers at the University of Oxford of US patient records found that semaglutide was associated with a lower risk of cognitive problems and nicotine dependence. It was designed to assess whether the drug could have negative effects on the brain and, instead, found the opposite.
GLP-1 drugs can have side effects, though, primarily gastrointestinal problems like nausea and vomiting. In the liraglutide trial in Alzheimer’s, those effects were most common.
The study received some funding from Novo Nordisk, in addition to the Alzheimer’s Society UK and others.
Although more work needs to be done to prove that GLP-1 drugs could help people with Alzheimer’s, Carrillo heralded the potential for the medicines to be used not just by themselves but potentially in combination with recently approved drugs that clear amyloid plaque buildups from the brain.
“There’s a lot of hope, not only for a positive semaglutide trial but also for the ability to be able to combine that with a monoclonal antibody FDA-approved today,” she said.