Study: GLP-1s could slow Alzheimer’s
Researchers say drugs might reduce memory and thinking problems
A popular new class of medications sheds pounds, treats diabetes and reduces heart disease risk. Can these drugs also protect the brain from memory and thinking problems?
People who took Novo Nordisk’s liraglutide for one year had an 18% slower cognitive decline compared with those who got a placebo, according to a study unveiled Tuesday at the Alzheimer’s Association International Conference.
Researchers cautioned the study did not recruit enough patients to draw broad conclusions, but the pharmaceutical company that sells liraglutide, Novo Nordisk, is studying the cognitive effects on a larger group of patients.
The study suggests the class of drugs known as GLP-1 agonists − approved for diabetes, weight loss and to reduce the risk of heart disease − also might protect the brain.
Dr. Paul Edison, a professor of science at Imperial College in London who led the study, was set to present more details about the research during a Tuesday afternoon session at the AAIC meeting in Philadelphia. The singlecenter study hasn’t been peer-reviewed by a medical journal.
The UK-based study enrolled 204 patients with mild to moderate Alzheimer’s disease who were randomly assigned to get a daily injection of liraglutide or a placebo for one year. Liraglutide is sold under the brand name Saxenda for weight loss and Victoza for diabetes treatment.
All patients had MRIs to check for brain volumes and PET scans to monitor glucose metabolism. The brain scans were done at the start of the Phase 2 study and repeated after one year. Study participants received cognitive tests at the start of the study, 24 weeks later and one year later.
The most common side effects among people who took liraglutide were nausea and stomach problems. About one in four people who experienced side effects reported gastrointestinal issues. Complaints of digestive issues are common among the millions of Americans who take GLP-1 agonists for weight loss or diabetes.
This category of drugs also includes the newer Novo Nordisk medications Ozempic for diabetes and Wegovy for weight loss, as well as Eli Lilly drugs Mounjaro for diabetes and Zepbound for weight loss.
Brains shrank less, memory loss slowed
The study didn’t meet its main goal, or endpoint, which was based on changes in the brain’s glucose metabolism rate. But it did report improvements in memory and other thinking skills among people who took the active drug.
Cognitive scores were calculated via a common test, called the Alzheimer’s disease assessment scale, which includes 18 measures of memory, comprehension, language and spatial orientation. The 79 study participants who completed one year of treatment had 18% less decline than 87 participants who got a placebo.
Brain scans showed those who received liraglutide lost nearly 50% less volume in the frontal, temporal, parietal and total gray matter − areas of the brain that control memory, learning, language and decision making.
“It leads us to really think about the promise of these types of new medications for Alzheimer’s disease or other types of dementia,” said Dr. Rebecca Edelmayer, senior director of scientific engagement for the Alzheimer’s Association.
Edison said the research is the first to suggest GLP-1 drugs might slow memory and thinking problems in Alzheimer’s patients.
“What it’s doing is providing some neuroprotective function,” Edison told USA TODAY. “If (patients) were to (get) the drug early on in the disease trajectory, that 18% over a period of time can have a significant benefit. But obviously we need to test that in the larger study.”
What study didn’t measure
Even though study participants received multiple brain scans, researchers didn’t check whether they had a measurable difference in amyloid-beta plaques, a hallmark of Alzheimer’s disease. Nor did researchers check for the protein tau, which cling together and form tangles in brain cells.
Drug companies largely have focused on attacking amyloid-beta as a way to slow Alzheimer’s, an incurable disease that afflicts 6.9 million Americans.
Earlier this month, the FDA approved Eli Lilly’s Alzheimer’s drug donanemab, shown in studies to slow the early stages of the disease. Last year, the FDA approved Eisai and Biogen’s drug Leqembi, which also slowed cognitive decline in people with early stages of the disease. Both drugs remove amyloid from the brains of Alzheimer’s patients.
Edison said his research team did not measure amyloid because they felt it would have asked too much from study participants, who already had to take daily injections as well as brain scans and medical assessments. He said a larger study involving an oral version of semaglutide will measure amyloid-beta and tau in patients.
A three-year clinical study of semaglutide, sold under the brand names Ozempic and Wegovy, is underway in more than 1,800 people with early Alzheimer’s disease.
Edison said the follow-up studies might provide more clues to how GLP-1 medications counter other Alzheimer’s factors such as brain inflammation and insulin resistance.
In animal studies, he noted these medications showed they might help combat the disease by reducing amyloid and protecting the connections between brain cells.
Because this study suggests liraglutide appears to protect the brain, Edison said the theory needs to be tested in a larger study over a longer period.
“The assumption is the trajectory of these changes will carry on over a period of time,” Edison said.
“Obviously, we need to test that, and that’s precisely what’s happening at the moment.”