GLP-1 Shows Protection Against Dementia in Phase 2b Trial
Liraglutide slowed the loss of volume in critical brain regions and cognitive decline in patients with mild Alzheimer's dementia.
The glucagon-like peptide-1 receptor agonist (GLP-1) liraglutide may slow cognitive decline and protect the brain in patients with mild Alzheimer’s disease, according to new data presented at the Alzheimer’s Association International Conference (AAIC) 2024, held July 28 to August 1 in Philadelphia, Pennsylvania.1
GLP-1 Shows Protection Against Dementia in Phase 2b Trial / Atthapon - stock.adobe.com
The study was funded by the Alzheimer’s Association’s Part the Cloud program, which provides research grants to investigators that are “addressing known and potential new aspects of the disease.” The program, established in 2012, has so far invested over $82 million to advance 68 different clinical trials.
READ MORE: Semaglutide Use Increases Risk of Optic Neuropathy
“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,” Maria C. Carrillo, PhD, chief science officer and medical affairs lead at the Alzheimer’s Association, said in a release.1 “This research provides hope that more options for changing the course of the disease are on the horizon.”
GLP-1s have proven to be effective medications for the management of type 2 diabetes. Newer research has also demonstrated their impact on weight loss, cardiovascular disease prevention and potential for decreasing the progression of chronic kidney disease.2 In animal models, GLP-1s have demonstrated neuroprotective effects, including improving memory function, delaying progressive decline in spatial memory, and influencing cognitive function.3
In the study presented at AAIC 2024, investigators from Imperial College London conducted a randomized, double-blind, placebo-controlled trial (NCT01843075) to evaluate the effects of liraglutide in patients with mild Alzheimer's dementia. The study cohort included 204 adult patients with mild Alzheimer’s disease who either received a daily subcutaneous injection of 1.8 mg liraglutide or placebo.
The patients were seen at 24 clinics throughout the United Kingdom and underwent MRI and PET scans before the study began to evaluate brain structure, volumes and glucose metabolism. Patients also took part in detailed memory testing. The primary study endpoint was change in the cerebral glucose metabolic rate in the cortical regions of the brain. Secondary endpoints included change in scores for clinical and cognitive measures, and endpoint of brain volume.
Although the study did not meet its primary endpoint, liraglutide showed statistically significant benefits in the key secondary endpoints. Investigators found that patients who received the therapy had nearly 50% less volume loss in several areas of the brain that are responsible for critical functions like memory, language and decision-making. In cognitive testing, which was conducted at weeks 24 and 52, patients receiving liraglutide had an 18% slower decline in cognitive function after 1 year compared to the placebo group.
“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” Paul Edison, MD, PhD, professor of science from Imperial College London Edison and lead researcher on the study, said in a release.1 “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.”
Although there were 25 serious adverse events in 18 patients, they were considered unlikely to be related to the study treatment. The most common adverse events during the study were gastrointestinal problems such as nausea.
“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 said in the release.1
READ MORE: Neurology Resource Center
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