Can a GLP-1 drug protect against cognitive decline? …C0NTINUE READING HERE >>>
Share on PinterestCan a GLP-1 drug help protect against cognitive decline? Early trials say ‘yes.’ Image credit: Halfpoint Images/Getty Images.Over the last year, the use of and interest in glucagon-like peptide-1 (GLP-1) receptor agonists has significantly increased.Scientists have been examining the use of the GLP-1 drug liraglutide to treat additional treatments other than type 2 diabetes and obesity. Researchers from Imperial College London have found that liraglutide may also help protect the brain from developing Alzheimer’s disease by reducing cognitive decline.
Over the last year, the use of and interest in glucagon-like peptide-1 (GLP-1) receptor agonists — such as Ozempic, Wegovy, and Zepbound — have skyrocketed.
Originally used to treat type 2 diabetes, GLP-1 drugs have recently become popular to assist in weight loss, either through off-label use or, in specific cases, as an FDA-approved weight loss medication.
One such GLP-1 medication is liraglutide, sold under the brand names Saxenda and Victoza.
In addition to use for the treatment of type 2 diabetes and obesity, previous research has also looked at using liraglutide to treat other conditions including polycystic ovary syndrome (PCOS), heart failure, nonalcoholic fatty liver disease, and liver fibrosis.
Now researchers from Imperial College London, in the United Kingdom, recently presented research at the Alzheimer’s Association International Conference 2024 reporting that liraglutide may also help protect the brain from developing Alzheimer’s disease by reducing cognitive decline.
Their study has not yet appeared in a peer-reviewed journal.
For this phase 2b clinical trial, researchers recruited 204 participants with mild Alzheimer’s disease who had been seen at 24 clinics around the U.K.
Before the start of the study, participants underwent magnetic resonance imaging (MRI) to evaluate their brain structure and volumes, PET scans, and cognitive function testing such as memory and spatial orientation.
For 1 year, half of the study participants were administered a dose of liraglutide while the other half received a placebo.
At the study’s 1-year conclusion, scientists discovered that participants receiving liraglutide had an 18% slower cognitive function decline compared to those who received the placebo.
“The study was not powered to show a change in the cognitive [memory] outcome measures,” Paul Edison, MD, PhD, professor of neuroscience in the Division of Neurology of the Faculty of Medicine at Imperial College London, and lead author of this study told Medical News Today.
“We were very encouraged by the fact that there was a significant slower reduction in cognitive function. This suggests that GLP-1 analogues have great potential to reduce the neurodegenerative process and improve cognitive function,” he added.
“Even though there has been some progress in treating Alzheimer’s disease with the developments in anti-amyloid therapy, we are in desperate need for new medications which could be widely used. Alzheimer’s disease is associated with amyloid deposition, tau formation, increased neuroinflammation, insulin resistance, and progressive neuronal damage. GLP-1 analogues have a unique property whereby it reduces neuroinflammation, reduces tau formation, reduces insulin resistance, reduces amyloid formation, and improves connection between the brain cells.”
– Paul Edison, MD, PhD
Edison and his team believe liraglutide’s brain protection may stem from causing a slower loss of brain volume.
In the study, participants who took liraglutide had almost 50% less volume loss in several areas of the brain, including the frontal cortex, temporal lobe, parietal lobe, and total gray matter, which are responsible for cognitive functions like memory, attention, understanding language, visual attention, and spatial perception.
“This demonstrates that GLP-1 analogues provide benefit by changing the underlying processes which cause memory problems,” Edison said. “Change in MRI volume could represent [the] combined effect of the drug on the underlying processes going on in the brain.”
However, “GLP-1 analogues should be tested in [a] larger number of patients in Phase 3 studies,” he cautioned.
“We are also performing studies to better understand how these drugs exerts its effect on the brain and to develop novel drugs which are specifically designed for Alzheimer’s disease,” Edison told us.
After reviewing this study, David Merrill, MD, PhD, a board-certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health, told MNT this is good news.
“While we know that healthy lifestyle habits like following a MIND diet and getting regular physical exercise reduce Alzheimer’s disease risk, not all patients and persons at risk for Alzheimer’s disease are ready or able to adhere to these long-term regimens,” Merrill explained.
“Medications like GLP-1 agonists may become critical tools in optimizing not only peripheral metabolism of blood sugar, but also work through multiple mechanisms in the brain to stave off memory loss in those at risk for dementia,” he noted.
“This class of drugs has been remarkable in working through multiple mechanisms to optimize not only body health but brain health as well,” Merrill continued.
” As the saying goes, there appears to be a ‘there there.’ It’s important that we continue to intentionally study the short and long-term outcomes of use of these meds explicitly in those at risk for and developing early stage Alzheimer’s disease and related dementias,” he advised.
Merrill said that combining these and other “silver bullet” drug candidates for Alzheimer’s disease prevention and treatment with healthy lifestyle interventions is a logical next step:
“I’d hope that as patients are given the hope and positive reinforcement of seeing their memory and health improve with drug use in the short run, that they’d then have the support and experiential coaching and education needed to transition to lifestyle-based habits like diet and exercise to maintain their gains. We need better health insurance coverage of non-MD services like those provided by not only licensed allied health providers — including physical therapists — but also PT aides, health coaches, and outpatient nutrition services. The needs are great but the coverage is currently not.”
MNT also spoke with Mir Ali, MD, a board-certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, about this study.
He told us that the study “was interesting because you don’t think of this type of medication as affecting Alzheimer’s, but the theory that it may be due to chronic inflammation and these medications may be helping with that makes sense.”
“If [researchers] can find further benefits to these [GLP-1] medications, that’s all the more reason to develop these further and find more effective ones. There are some that I’ve read about that are in the pipeline that actually may work even better than these medications, so finding broader indications for these things is useful, although that may lead to a bigger shortage,” Ali commented.
“It would be nice to see more detailed research about how these medications might actually be helping Alzheimer’s patients,” he continued. “They touched on it to some extent in this article, but they need to do a lot more research looking at if they are directly affecting the brain or if it’s the weight loss and reduction in chronic inflammation that’s actually helping. So a lot more research needs to be done as a mechanism of action for this effect.”
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