Promising New Data Support GLP-1s for Dementia Prevention

A brand recent peer helps the functionality to repurpose glucagon-bask in peptide 1 (GLP-1) receptor agonists, passe to address form 2 diabetes and weight problems, for dementia prevention.
Within the section 2b ELAD clinical trial, adults with early-stage Alzheimer’s illness (AD) taking the GLP-1 receptor agonist liraglutide exhibited slower decline in reminiscence and pondering and experienced less mind atrophy over one year compared with placebo.
“The slower loss of mind quantity suggests liraglutide protects the mind, great bask in statins protect the center,” peer chief Paul Edison, MD, PhD, with Imperial College London, London, United Kingdom, said in a commentary.
“Whereas additional be taught is wished, liraglutide may perhaps likely perhaps also match thru diverse mechanisms, equivalent to reducing inflammation in the mind, reducing insulin resistance and the poisonous outcomes of Alzheimer’s biomarkers amyloid-beta and tau, and bettering how the mind’s nerve cells discuss,” Edison said.
He presented the peer outcomes on July 30 on the Alzheimer’s Affiliation Global Convention 2024.
Mind Advantages
Liraglutide has beforehand demonstrated promising neuroprotective outcomes in animal objects of AD and epidemiologic studies.
Within the ELAD trial, 204 patients with comfy to moderate AD had been randomly allocated (1:1) to a day-to-day subcutaneous injection of up to 1.8 mg of liraglutide or placebo for one year; 80 patients in the liraglutide crew and 89 in the placebo crew done the peer.
Mind MRI became performed at baseline and at one year, alongside with neuropsychometric evaluate and 18F-fludeoxyglucose PET.
The peer’s well-known endpoint — commerce in the cerebral glucose metabolic price in the cortical regions of the mind (hippocampus, medial temporal lobe, and posterior cingulate) — became no longer met.
Then again, patients taking liraglutide experienced a serious slowing of cognitive decline, compared with placebo crew (P = .01), which became a key secondary , calculated as a composite rating of 18 diversified tests of reminiscence, comprehension, language, and spatial orientation.
Although the peer became no longer powered to evaluate cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive feature over one year compared with those on placebo, Edison reported.
As well, patients treated with liraglutide had virtually 50% less quantity loss in several areas of the mind interesting about reminiscence, language, and resolution-making, including frontal, temporal, parietal, and total grey topic, as measured by MRI.
Liraglutide day-to-day subcutaneous injections had been safe and properly tolerated in patients with AD, Edison reported. There had been 25 serious aspect outcomes — 18 in the placebo crew and 7 in the liraglutide crew, — and most had been thought to be no longer going to be associated to the peer remedy. There had been no deaths.
Promising, Preliminary
This peer reveals a sure attain of liraglutide on the mind by manner of “slowing down of mind atrophy and slowing down the price of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t interesting about the peer.
Heather Snyder, PhD, vice-president of scientific and scientific relatives on the Alzheimer’s Affiliation, said it is “intelligent” to scrutinize slowing of mind quantity loss and some cognitive aid “especially because the peer became no longer powered necessarily to scrutinize some of those changes.
The indisputable reality that they did look these changes on this puny peer affords a window into what may perhaps likely perhaps also happen, however we certainly want better section 3 studies,” she told Medscape Medical Files.
In a commentary from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Affiliation and crew chief on the UK Dementia Evaluate Institute, called the facts “promising.”
“There are sure links from stable files in the field between vascular effort factors including diabetes and weight problems being associated with increased effort of dementia. The GLP-1 drug have to restful abet decrease these effort factors as properly as potentially straight protecting mind cells,” Spires-Jones said.
Then again, she said “extra be taught in better trials is wished to confirm whether this form of remedy will most definitely be effective in of us with Alzheimer’s illness.”
Stephen Evans, MSc, emeritus professor, London College of Hygiene and Tropical Treatment, London, United Kingdom, illustrious that the repurposing of pills is “a truly considerable avenue of be taught however there may perhaps be loads of uncertainty here.”
He cautioned that the “50% mind quantity commerce may perhaps likely perhaps also no longer translate to particular cognitive outcomes, and reporting simplest on those who done the plump 52 weeks of remedy may perhaps likely perhaps also bring bias into the implications. It sounds bask in it is price pursuing a better trial, however these outcomes can no longer gift that liraglutide can protect in opposition to dementia.”
The continuing section 3 EVOKE trial is investigating the implications of the GLP-1 receptor agonist semaglutide in early AD.
Funding for the peer became offered by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk AS, John and Lucille Van Geest Foundation, and the Nationwide Institute for Smartly being and Care Evaluate Biomedical Evaluate Centre. Edison, Fillit, Snyder, Evans, Spires-Jones had no relevant conflicts of curiosity.