Novo Nordisk's liraglutide GLP-1 may slow the progression of Alzheimer's


A box of the drug Victoza, manufactured by Novo Nordisk Pharmaceutical, sits on a pharmacy counter in Provo, Utah, January 9, 2020.

George Frey | Reuters

An older, once-daily drug for diabetes and obesity New Nordisk A drug called liraglutide may slow the progression of Alzheimer's disease by protecting patients' brains, according to data from a mid-stage trial published Tuesday.

Novo Nordisk sells liraglutide as a diabetes and obesity drug under the brand names Victoza and Saxenda, respectively. Quarterly sales of these daily injections have been declining as patients turn to the Danish drugmaker's more popular weekly injections, Ozempic for diabetes and Wegovy for weight loss.

The results add to growing evidence that the popular class of obesity and diabetes drugs, called GLP-1, may have important health benefits beyond promoting weight loss and regulating blood sugar. As demand for GLP-1 soared over the past two years, Novo Nordisk and rival Novo Nordisk have been seeking to boost their competitiveness. Eli Lilly They have been studying the potential of their drugs in patients with chronic diseases ranging from fatty liver disease to sleep apnea.

Researchers at Imperial College London followed more than 200 UK patients with mild to moderate Alzheimer's disease, who were randomly assigned to receive a daily injection of liraglutide or a placebo. The study was partly funded by Novo Nordisk.

Patients who received liraglutide had an 18% slower decline in cognitive function after one year of treatment compared to those who received placebo.

The phase two trial found that liraglutide slowed the shrinkage of certain parts of the brain that are critical for memory, decision-making, learning and language by nearly 50% compared with placebo, based on MRI scans. Alzheimer's disease often causes the brain to shrink as the disease progresses because crucial nerve cells break down and stop working properly.

The researchers presented the results Tuesday at the Alzheimer's Association International Conference in Philadelphia, the world's largest meeting for dementia research.

Alzheimer's is the most common form of dementia, a general term for loss of memory, language and other thinking abilities.

Brian B. Bettencourt | Toronto Star | Getty Images

The new data demonstrate the diversity of therapies being developed or tested for Alzheimer's disease, paving the way for new and potentially more personalized approaches to treating the disease, said Dr. Heather Snyder, vice president of medical and scientific relations for the Alzheimer's Association.

According to the Alzheimer's Association, nearly 7 million Americans suffer from the disease, which is the fifth leading cause of death among adults over 65. It is estimated that by 2050, the number of Alzheimer's patients in the United States will increase to nearly 13 million.

Alzheimer's treatment has made great strides over the past year, with two new drugs approved that have been shown to slow the progression of the disease by targeting a toxic brain protein called amyloid, a hallmark of the disease. They include Eli Lilly's Kisunla and Leqembi from Biogen and Eisai.

Snyder told CNBC on Tuesday that the new data “opens the door” for scientists to explore combining such amyloid-targeting drugs with GLP-1 like liraglutide.

Importantly, existing research shows that GLP-1s do not carry the risk of brain swelling and bleeding, two side effects that have been linked to Leqembi and Kisunla. Patients receiving these amyloid-targeting treatments undergo routine MRIs to monitor for those side effects.

In the mid-stage trial, patients receiving liraglutide more frequently experienced gastrointestinal side effects associated with other GLP-1s, such as nausea.

That may be an advantage of using GLP-1 to treat Alzheimer's patients, only a small proportion of whom currently receive drugs targeting amyloid.

“Having a drug with a very good safety profile that can be used widely will change the field significantly,” Dr. Paul Edison, professor of neuroscience at Imperial College London and senior author of the trial, told CNBC.

He said that GLP-1s, if approved for Alzheimer's, “could be given virtually anywhere in the world without a lot of monitoring” for side effects, showing there is “a lot of potential” for such drugs.

But more research is needed, he noted.

Edison is participating in Novo Nordisk's Phase 3 EVOKE and EVOKE+ trials. The ongoing EVOKE trial is examining semaglutide, the active ingredient in Wegovy and Ozempic, in nearly 2,000 Alzheimer's patients.

In a statement, Novo Nordisk said it welcomes independent research investigating its GLP-1s as treatments for other conditions, but noted that such products are not currently approved for Alzheimer's disease.

Liraglutide trial details

Mr. Bobby Pugh, 91, cares for his wife Bessie Pugh, 90, an Alzheimer's patient at Ave Maria Home, an assisted living facility for seniors, in Bartlett, Tennessee, U.S., on September 13, 2023.

Karen Pulfer Focht | Reuters

Measures of cognitive function and brain volume were not the primary objectives of the study.

The main goal of the trial was to measure how much glucose the brain consumes, which is important for assessing cognitive function. As Alzheimer's disease progresses, the so-called glucose metabolic rate in certain parts of the brain decreases.

Edison said he and his team believe they did not have enough trial participants to show a significant change in that rate, but he found it encouraging that liraglutide met the study's second goal of showing a benefit in cognitive function, along with another goal of a change in brain volume.

These findings suggest that GLP-1s like liraglutide may protect the brain, Edison said.

“I think showing cognitive enhancement is the key, because that's what patients are interested in,” he told CNBC.

He said liraglutide likely accomplishes that through several ways, such as reducing inflammation in the brain, improving the way nerve cells in the brain communicate and reducing insulin resistance, as well as reducing Two hallmarks of Alzheimer's disease: toxic proteins called amyloid plaque and tau.

More research is needed to confirm this, Edison said.

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