Semaglutide, the active ingredient in Ozempic and Wegovy, appeared to reduce the risk of Alzheimer’s disease in people with Type 2 diabetes, according to a study published Thursday in the journal Alzheimer’s & Dementia.
The study adds to evidence that GLP-1 drugs — the class of medications that also includes Mounjaro and Zepbound — may benefit the brain.
In July, research presented at the Alzheimer’s Association International Conference found that a GLP-1 drug similar to semaglutide — called liraglutide — was linked to slower cognitive decline in patients with mild Alzheimer’s disease who didn’t have diabetes. Another study, published in August, found that semaglutide appeared to cut the risk of dementia in people with Type 2 diabetes. Type 2 diabetes is a risk factor for dementia and Alzheimer’s.
Novo Nordisk, which makes Ozempic and Wegovy, is running two phase 3 clinical trials comparing semaglutide to a placebo in more than 3,000 patients with mild cognitive impairment or early-stage Alzheimer’s disease. The trial results are expected to be released sometime next year.
If those trial results are positive, semaglutide “would be a game changer, adding a whole new treatment option that we didn’t previously have in our tool kit,” said Dr. Stephen Salloway, a professor of neurology at Warren Alpert Medical School of Brown University in Rhode Island.
“If this actually works, it would be huge,” Salloway said.
How did semaglutide perform?
The new study compared semaglutide to seven other diabetes drugs, including metformin, insulin and older GLP-1 drugs, including liraglutide.
The researchers looked at three years of medical records of more than 1 million patients with Type 2 diabetes ages 60 and up who had just started on one of the drugs. Participants also had to have at least one other underlying condition — such as obesity, hypertension or heart disease — and couldn’t have used a diabetes drug within the past six months.
The study found that patients prescribed semaglutide had a significantly lower risk for Alzheimer’s disease than those who had taken one of the seven other diabetes drugs. The results were consistent across gender, age and weight.
The biggest difference was seen when comparing patients who took semaglutide to those who took insulin: Semaglutide patients had a 70% lower risk of Alzheimer’s, the study found.
Rong Xu, the senior study author and the director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University School of Medicine in Ohio, said that semaglutide also led to a significantly lower risk compared to older GLP-1 drugs including liraglutide — a finding she was surprised by.
The highest dose Ozempic comes in is 2 milligram dose; Wegovy is available in a higher dose, 2.4 mg. The patients in the study on semaglutide were prescribed Ozempic, Xu said.
“If there is a higher dose form, are we going to see an even stronger effect?” Xu said.
How could GLP-1s help?
There is no cure for Alzheimer’s disease.
The Food and Drug Administration has approved two treatments — Biogen’s Leqembi and Lilly’s Kisunla — that marginally slow the progression of the illness by targeting the disease’s hallmark amyloid plaques in the brain. However, they’re pricey and can come with serious side effects, including brain swelling and brain bleeding.
If semaglutide were found in clinical trials to reduce the risk of the disease, it could potentially be the first preventive treatment.
In a statement, a Novo Nordisk spokesperson said the company “welcomes independent research investigating the safety, efficacy, and clinical utility of our products.”
Researchers still don’t know exactly how semaglutide protects the brain against Alzheimer’s disease and by how much, Salloway said.
However, studies have shown that the drug has positive effects against inflammation, diabetes, obesity and heart disease, all of which are risk factors for dementia and Alzheimer’s, he said.
“Besides weight loss, of course, everything they’ve been trying for they’ve been working for,” Salloway said. “They lower the rate of heart attack, they control diabetes, they lower the rate of stroke, they control renal disease, so numerous positive effects.”
Donna Wilcock, the editor-in-chief of Alzheimer’s & Dementia and a professor of neurology at Indiana University School of Medicine, said there’s been increasing interest that GLP-1 drugs may have an effect on Alzheimer’s.
“They improve the health of the blood vessels, which we know are impacted in Alzheimer’s disease, as well as cerebral small vessel disease, a common comorbidity with Alzheimer’s and other neurodegenerative processes,” Wilcock said. “It is unclear in this study whether the benefits are independent from the impact on Type 2 diabetes — a risk factor for dementia — or whether the benefits are secondary to improving Type 2 diabetes.”
Dr. Alberto Espay, a neurologist at the University of Cincinnati College of Medicine, stressed that more research is still needed to determine whether the drugs actually work against Alzheimer’s.
Alzheimer’s is thought to be a condition of multiple diseases, Espay said, so one treatment may not work for everyone.
What’s more, early studies also suggested that statins, nonsteroidal anti-inflammatory drugs and insulin had a positive effect on Alzheimer’s, but none of those treatments panned out.
“Just as with statins, NSAIDs and insulin, we should be cautious about claiming semaglutide can treat or prevent Alzheimer’s based on this study alone,” Espay said.
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