Liraglutide May Shield Against Dementia

A new study suggests that a glucagon-like peptide-1 (GLP-1) drug could offer protection against cognitive decline by safeguarding brain health, according to data from a Phase 2b clinical trial disclosed at the Alzheimer's Association International Conference® (AAIC®) 2024 in Philadelphia. 

GLP-1 receptor agonists, which imitate the hormone glucagon-like peptide naturally released by the stomach after meals, are known to aid in diabetes management, weight loss, and reducing risks of heart diseases, strokes, and kidney conditions. Findings from animal models of Alzheimer's disease indicate that these drugs may have neuroprotective properties, reduce early amyloid forms, normalize glucose processing in the brain, and enhance memory and learning. Liraglutide, a GLP-1 drug developed by Novo Nordisk, is believed to work through various mechanisms within the brain.

The recent research presented at AAIC 2024 points to liraglutide's potential in protecting the brains of people with mild Alzheimer’s disease and mitigating cognitive decline. The trial results indicate that after one year of treatment, liraglutide may reduce the shrinkage of brain areas essential for memory, learning, language, and decision-making by as much as 18% compared to a placebo.

"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," stated Maria C. Carrillo, Ph.D., the Alzheimer's Association chief science officer and medical affairs lead. She emphasized that repurposing drugs already approved for other conditions is advantageous due to the existing data on their real-world effectiveness and known side effects.

The Alzheimer's Association’s Part the Cloud research grants program has allocated over $82 million to support 68 clinical trials targeting numerous compounds, including repurposed drugs, which address both established and new aspects of Alzheimer’s disease.

The Evaluating the Effects of the Novel GLP-1 Analogue Liraglutide in Alzheimer's Disease (ELAD) trial, led by Professor Paul Edison, M.D., Ph.D., from Imperial College London, was a randomized, double-blind, placebo-controlled study. It involved 204 patients with mild Alzheimer's disease across 24 clinics in the UK. Participants received daily subcutaneous injections for a year, with half of them receiving up to 1.8 mg of liraglutide and the other half a placebo. Before the study began, patients underwent MRI scans to assess brain structure, glucose metabolism PET scans, and detailed memory tests. These evaluations were repeated at the study's end, alongside regular safety visits.

Though the study’s primary endpoint — change in the cerebral glucose metabolic rate in cortical brain regions — was not met, secondary endpoints demonstrated statistically significant benefits. Liraglutide appeared to slow the loss of brain volume in areas crucial for cognitive functions.

"The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart," Dr. Edison explained. He noted that further research is necessary but suggested that liraglutide might work by reducing brain inflammation, lowering insulin resistance, diminishing the toxic effects of Alzheimer's biomarkers amyloid-beta and tau, and improving nerve cell communication in the brain.

In the study, patients receiving liraglutide exhibited nearly 50% less volume loss in several brain regions, including the frontal, temporal, and parietal areas, which are responsible for memory, language, and decision-making. Cognitive testing revealed that those on liraglutide experienced an 18% slower decline in cognitive function over a year compared to those on the placebo.

Gastrointestinal issues, particularly nausea, were the most common side effects, amounting to 25.5% of all adverse events in the liraglutide group. Serious side effects occurred in 17.6% of the placebo group and 6.9% of the treatment group, with most considered unlikely to be related to the study treatment, according to Dr. Edison.

Current late-stage clinical trials of GLP-1 analogues, such as the EVOKE Plus trial involving semaglutide in over 1,800 people with early Alzheimer's, are well-positioned to further test these findings.

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