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DAYTON – Liraglutide, a glucagon-like peptide-1 (GLP-1) drug appears to slow cognitive decline by protecting the brain, according to Phase 2b clinical trial data reported today at the Alzheimer’s Association International Conference® (AAIC®) 2024.
GLP-1 receptor agonists, which mimic the natural hormone glucagon-like peptide released by the stomach after eating, can help people manage diabetes, lose weight and lower their risk of heart disease, stroke and kidney disease. Research in animal models of Alzheimer’s disease suggests these drugs may have neuroprotective effects, reduce early forms of amyloid, normalize the brain’s processing of glucose, and improve memory and learning. Liraglutide (Novo Nordisk) likely works by multiple mechanisms in the brain.
This new research suggests liraglutide may protect the brains of people with mild Alzheimer’s disease and reduce cognitive decline by as much as 18% after one year of treatment compared to placebo by slowing the shrinking of the parts of the brain that are vital for memory, learning, language and decision-making.
“We are in an era of unprecedented promise, with new treatments in various stages of development that slow or may possibly prevent cognitive decline due to Alzheimer’s disease,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer and medical affairs lead. “This research provides hope that more options for changing the course of the disease are on the horizon.
“Repurposing drugs already approved for other conditions has the advantage of providing data and experience from previous research and practical use — so we already know a lot about real-world effectiveness in other diseases and side effects,” Carrillo added.
The randomized, double-blind, placebo-controlled trial led by Prof. Paul Edison, M.D., Ph.D., professor of science from Imperial College London, included 204 patients with mild Alzheimer’s disease at 24 clinics throughout the United Kingdom. Each received a daily subcutaneous injection for one year: half received liraglutide and half received a placebo. Before and after the study, all patients had magnetic resonance imaging (MRI) to evaluate brain structure and volumes, glucose metabolism PET scans and detailed memory testing.
The study’s primary endpoint was change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe and posterior cingulate), which was not met. However, the secondary endpoint of change in scores for clinical and cognitive measures and the exploratory endpoint of brain volume showed statistically significant benefit.
“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” said Dr. Edison. “While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid-beta and tau, and improving how the brain’s nerve cells communicate.”
Edison added that those in the study who received liraglutide had nearly 50% less volume loss in several areas of the brain, including frontal, temporal, parietal and total gray matter, as measured by MRI. These areas are responsible for a variety of critical functions that often are affected by Alzheimer’s disease, including memory, language and decision-making.
Researchers conducted cognitive testing in 204 patients — before treatment and at 24 and 52 weeks. Although the study was not powered to assess cognitive changes, researchers found that patients who received liraglutide had an 18% slower decline in cognitive function in a year compared to those who got the placebo.
There are 236,200 Ohioans 65 and older living with Alzheimer’s disease, according to the Alzheimer’s Association 2024 Alzheimer’s Disease Facts and Figures. More than 4,900 Ohioans died from Alzheimer’s in 2021 (the most recent year for state-by-state data). A total of 414,000 Ohio caregivers provide 624 million hours of unpaid care each year valued at over $11.4 billion.
To learn more about Alzheimer’s or other dementia and to access free support and resources, visit alz.org/dayton or call the Miami Valley Chapter at 937.291.3332 or the 24/7 Helpline at 800-272-3900.
Story from Alzheimer’s Association, Miami Valley chapter in Dayton.
