CAN A POPULAR WEIGHT-LOSS DRUG REDUCE RISK OF ALZHEIMER’S?

Semaglutide, the active ingredient in popular blood sugar control and weight loss drugs such as Ozempic and Wegovy, can reduce the risk of Alzheimer’s disease (AD) in people with type 2 diabetes, a new study shows.

Alzheimer’s causes a gradual decline in memory, thinking, behaviour, and social skills, and it is the most common cause of dementia. According to the new study published in the journal Alzheimer’s & Dementia on Thursday, semaglutide was found to significantly lower the risk of developing AD compared to other diabetes medicines. Specifically, it was found to reduce the risk of a first-time Alzheimer’s diagnosis by 40% to 70%.

“These results were similar for older patients, both genders, and those with and without obesity. Cumulative incidence curves [of semaglutide and other diabetes medicine] began to diverge within 30 days, and continued to separate thereafter, indicating semaglutide’s potential to delay or slow Alzheimer’s Disease development with sustained effects,” the study said.

A promising study

Researchers analysed health records of over a million patients in the US with type 2 diabetes to see how semaglutide affects the risk of developing AD. They compared semaglutide to seven other diabetes medications, and tracked the patients for up to three years to see if they were diagnosed with Alzheimer’s. The other diabetes drugs used in the study included metformin, insulin, and older GLP-1 drugs like liraglutide.

Using specific statistical methods, they studied the time it took for Alzheimer’s to be diagnosed in these patients, if at all. The study found that patients prescribed semaglutide had a significantly lower risk of AD than those who had taken one of the seven other diabetes drugs.

The most notable difference with regards to AD incidence was seen between patients who took semaglutide and those who took insulin, with semaglutide patients boasting a 70% lower risk of developing Alzheimer’s.

Semaglutide also outperformed its predecessor liraglutide. The study’s senior author Rong Xu, the director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University School of Medicine in Ohio, speculated based on this finding that more potent GLP-1 RA drugs might have an even stronger effect in combating Alzheimer’s.

“If there is a higher dose form, are we going to see an even stronger effect?” Xu said in an interview to NBC.

Science behind findings

The study said GLP-1 RAs, a group of drug which includes semaglutide, might help protect brain function. Early research on semaglutide identifies a number of ways in which it might benefit the brain such as lowering toxic effects of certain proteins linked to AD, improving how brain cells use glucose for energy, and reducing the buildup of harmful plaques and tangles associated with Alzheimer’s.

“Semaglutide reduces neuro-inflammation, which is commonly linked to Alzheimer’s. It helps stabilise blood sugar levels, limiting oxidative stress or cell damage and enhancing cellular energy. This action can protect neurons from degeneration, a hallmark of Alzheimer’s and other neurodegenerative diseases,” Dr (Prof) M V Padma Srivastava,  chairperson, Neurology, Paras Health, Gurugram, told The Indian Express.

“The study adds to our understanding of how blood glucose control via GLP-1 may offer brain-protective effects…[and] shows that effective blood glucose management and inflammation control are critical in Alzheimer’s progression,” she said.

Potential implications

The US Food and Drug Administration (FDA) has approved two treatments — Biogen’s Leqembi and Eli Lilly’s Kisunla — that marginally slow the progression of AD by targeting the disease’s hallmark amyloid plaques in the brain. But these can cause serious side effects, including brain swelling and brain bleeding. Traditionally, Alzheimer’s has been managed largely using cognitive and lifestyle interventions.

This is what makes the latest research, which introduces a new therapeutic pathway for treating Alzheimer, potentially ground-breaking. “By demonstrating that GLP-1 drugs can mitigate some risk factors for Alzheimer’s, the study suggests a dual-purpose use for these drugs: managing diabetes and offering a preventive mechanism for dementia,” Dr Srivastava said.

For India, this is particularly significant. The country boasts among the highest global rates of type 2 diabetes, which is associated with a higher risk of cognitive decline. This is because type 2 diabetes results in chronic insulin resistance, higher levels of inflammation, oxidative stress in the brain — all of which lead to impaired glucose metabolism in the brain, resulting in cognitive decline and neuron damage over time.

“GLP-1 drugs can delay or reduce dementia symptoms in diabetic patients, thus offering a preventive strategy where few currently exist,” according to Dr Srivastava. “Since Alzheimer’s rates are also rising among India’s ageing population, this research could be transformative,” she said.

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2024-10-25T22:41:09Z