Weight loss drugs could help to slow progression of Alzheimer's disease

Despite setback in NovoNordisk research, other GLP-1 medications have produced promising results

Weight loss drugs could help with managing the impact of Alzheimer's disease, a study has shown. Getty Images

Weight loss drugs may still help to fight against Alzheimer’s disease, despite a study by the manufacturer of Ozempic showing negative results.

NovoNordisk’s chief executive Mike Doustdar said the Danish company had ended research into how powerful GLP-1 drugs may slow Alzheimer’s progression, after disappointing results from a two-year study.

Semaglutide is found in the company’s two diabetes drugs, Ozempic and Rybelsus, and its weight loss drug Wegovy.

Results from an international clinical trial led by Imperial College London suggests a similar GLP-1 drug used for Type 2 diabetes, liraglutide, could reduce brain shrinkage, slowing cognitive decline in Alzheimer’s disease. In a study of 204 people with the condition, liraglutide slowed volume loss by half and an 18 per cent beneficial effect on cognition.

About 40 per cent of those who took part were women, with an average age of 71. At the start of the trial, all subjects reported similar levels of memory and thinking ability after completing cognitive tests.

Prof Paul Edison, the study’s chief investigator at Imperial College London, said liraglutide showed promise in repairing the brain pathways that lead to cognitive decline.

“Alzheimer’s disease is not purely a protein-accumulation disorder,” said Prof Edison. “It is caused by multiple changes happening in the brain: abnormal protein deposition, brain inflammation, impaired function of synapses, impaired function of microglia and astrocytes, and impaired insulin resistance.

“Drugs that repair these pathways could transform the field. This trial is important because it tests a completely different therapeutic strategy in Alzheimer’s disease – one that does not rely solely on targeting amyloid.”

Safe treatment

The study showed liraglutide was generally safe for the treatment of individuals with Alzheimer’s. Side effects included gastrointestinal issues and weight loss of about 5 per cent to 10 per cent.

Alzheimer’s remains the leading cause of dementia worldwide, affecting more than 55 million people. Despite decades of research, effective disease-modifying therapies remain limited, and treatments for amyloid accumulation alone have produced modest benefits.

Amyloid is the sticky plaque that builds up over time in the brain, disrupting communication between nerve cells and leading to memory loss. The clinical trial into the potential benefits of liraglutide have been published in the Nature journal.

By treating several processes occurring in Alzheimer’s disease like abnormal protein deposits in the brain and inflammation, they represent a fundamentally different approach to care. New drugs developed to treat Alzheimer’s, such as lecanemab and donanemab, are priced at about $40,000 for an annual supply.

The high costs mean they will remain out of reach for the majority, despite showing positive signs of slowing cognitive decline in the early stages of dementia. Some national health systems, such as the UK's National Health Service, have deemed them too costly, but they are available in the US, Australia and Canada.

GLP-1 receptor agonists such as liraglutide, originally developed for diabetes, have demonstrated neuroprotective effects in laboratory models.

As the drug is already approved, making it available it for Alzheimer’s disease could be significantly faster than developing a new therapy. At about $400 for a month-long supply, the drug is also more affordable.

“The ability to repurpose a drug with good safety data is a major advantage,” said Prof Edison. “We are not starting from zero. Our findings provide some of the strongest evidence yet that GLP-1 treatments could modify the disease process in Alzheimer’s disease.”

Fast track existing drugs

Scientists and experts from the Davos Alzheimer’s Collaborative, an international initiative to promote brain health, recently met UAE health officials to discuss ways to improve patient care and maximise the potential of new dementia drugs.

DAC founding chairman George Vradenburg said there was huge untapped potential in GLP-1 drugs.

“Taken together, the emerging evidence from Novo Nordisk’s semaglutide programme and the new findings on liraglutide reinforce a critical message: targeting metabolic pathways may hold real promise for Alzheimer’s, but we are still early in understanding where, when, and for whom these therapies can make a difference,” he said.

“The continued investigation of this approach underscores the importance of pressing forward on a broader, multi-pathway strategy that links metabolic health to inflammation, vascular function, and other upstream processes shaping lifelong brain health.”

Mr Vradenburg said up to 65 per cent of dementia cases could be prevented by taking care of your brain through good diet, exercise, mental exercises and sleep.

George Vradenburg, executive vice president of Davos Alzheimer’s Collaborative. Ryan Lim for The National

New drugs can also play a major role, he said.

“At the Davos Alzheimer’s Collaborative, we are advancing this agenda by expanding earlier detection, strengthening globally representative research, and accelerating prevention efforts in primary care settings around the world,” Mr Vradenburg said.

“As more data becomes available, we will assess how these metabolic-focused interventions fit into a wider architecture of earlier action, diverse biological approaches, and health-system readiness. The direction is clear: innovation is accelerating, and we must keep pushing across all fronts to change the trajectory of this disease.”