Weight-loss drugs could tackle Alzheimer’s – study
New review shows comprehensive evidence of impact of GLP-1 receptor agonists
A new study has found comprehensive evidence that ‘weight-loss’ GLP-1 receptor agonists such as semaglutide are effective in tackling the biological drivers of Alzheimer’s disease.
The study, published in the journal Molecular and Cellular Neuroscience, examined 30 preclinical studies investigating the effects of four GLP-1 receptor agonists – liraglutide; semaglutide; exenatide; and dulaglutide – on Alzheimer’s disease pathology.
The researchers, from Anglia Ruskin University (ARU), found consistent evidence from animal and cell studies that these drugs, commonly prescribed for people living with type 2 diabetes, reduce the buildup of amyloid‑beta and tau, the two hallmark proteins linked to the development and progression of Alzheimer’s.
The review found 22 studies showed reductions in amyloid‑beta, a protein that forms sticky plaques in the brain. 19 studies found reductions in hyperphosphorylated tau, the form of tau protein that creates harmful tangles within neurons. Liraglutide, the most extensively studied drug, consistently reduced both amyloid‑beta and tau pathology.
Dulaglutide and semaglutide also demonstrated positive effects on these proteins, though fewer studies were available. Exenatide studies yielded mixed results, with some showing reductions in amyloid or tau and others showing no effect.
Evidence in humans is still emerging. Of the two clinical trials that featured in the study, a 26‑week trial of liraglutide found no reduction in amyloid levels or cognitive improvement, but did show preservation of brain glucose metabolism, an indicator of neuronal function. An 18‑month trial of exenatide showed no significant changes in amyloid or tau in cerebrospinal fluid – the clear liquid that surrounds and protects the brain – but did reduce amyloid‑beta in extracellular vesicles, a potential early biomarker.
Alzheimer’s disease is the most common form of dementia in the UK, affecting around 900,000 people. The number is expected to rise significantly over the next decade. Despite decades of research, effective treatments remain limited.
“This new review provides one of the most comprehensive analyses so far of how GLP‑1 drugs interact with the underlying mechanisms of Alzheimer’s.
“Our study highlights several biological pathways by which GLP‑1 drugs may influence Alzheimer’s, including reducing inflammation, improving insulin signalling in the brain, and altering enzymes involved in the production of amyloid‑beta.
“Whilst human studies demonstrating an impact on cognitive decline are still lacking, the current evidence points towards these drugs having a preventative effect, rather than in patients with established cognitive impairment.
“With more than three‑quarters of preclinical studies showing reductions in amyloid‑beta or tau, and early signals emerging from studies on humans, GLP‑1 drugs remain strong candidates for future Alzheimer’s prevention trials. Larger, early‑stage clinical trials are now needed to determine whether these promising signs actually translate into tangible benefits for patients.”
Lead author Dr Simon Cork, Physiology lead at Anglia Ruskin University’s School of Medicine