Novo Nordisk GLP-1 liraglutide may slow Alzheimer’s progression

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

Novo Nordisk sells liraglutide as a diabetes and obesity drug under the brand names Victoza and Saxenda, respectively. Quarterly sales of those daily injections have been declining as patients shift toward the Danish drugmaker’s blockbuster weekly injections, Ozempic for diabetes and Wegovy for weight loss.

The results add to growing evidence that the highly popular class of obesity and diabetes medications called GLP-1s may have significant health benefits beyond promoting weight loss and regulating blood sugar. As GLP-1 demand skyrocketed over the last two years, Novo Nordisk and rival Eli Lilly have been studying their drugs’ potential in patients with chronic conditions ranging from fatty liver disease to sleep apnea. 

Researchers from the Imperial College London followed more than 200 patients in the U.K. with mild to moderate Alzheimer’s who were randomly assigned to receive either 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 the placebo. 

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

Researchers presented the results on Tuesday at the Alzheimer’s Association International Conference in Philadelphia, the world’s largest meeting for dementia research. 

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

Nearly 7 million Americans have the condition, the fifth-leading cause of death for adults over 65, according to the Alzheimer’s Association. By 2050, the number of Alzheimer’s patients is projected to rise to almost 13 million in the U.S.

The Alzheimer’s treatment space reached a breakthrough over the last year, with two newly cleared drugs proven to slow disease progression by targeting a toxic protein in the brain called amyloid, a hallmark of the condition. That includes Kisunla from Eli Lilly and Leqembi from Biogen and Eisai. 

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

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

In the mid-stage trial, patients who received liraglutide most commonly experienced gastrointestinal side effects associated with other GLP-1s, such as nausea. 

That may be one advantage of using GLP-1s to treat Alzheimer’s patients – only a small share of whom are currently receiving amyloid-targeting drugs. 

“Having a drug which has got a very good safety profile and could be used widely – it will change the field significantly,” Dr. Paul Edison, professor of neuroscience at the Imperial College London and the trial’s lead author, told CNBC. 

He said GLP-1s, if approved for Alzheimer’s, “could be administered pretty much anywhere in the world without a huge amount of monitoring” for side effects, which shows that there is “a great potential” for those drugs. 

But more research is needed, he noted. 

Edison is involved in Novo Nordisk’s phase three “EVOKE” and “EVOKE+” trials. The ongoing EVOKE 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 those products are not currently approved for Alzheimer’s disease.

The trial’s primary goal was measuring 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 declines. 

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

Those findings suggest that GLP-1s such as liraglutide can protect the brain, Edison noted. 

“I think demonstrating that cognitive improvement is the key, because that is what the patients are interested in,” he told CNBC. 

He said liraglutide likely achieves that through various ways, such as reducing inflammation in the brain, improving how the brain’s nerve cells communicate and lowering 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 that, Edison said.