Over the past few years, scientists have learned that Ozempic and related drugs developed to treat Type 2 diabetes can improve the health of the liver, kidney and heart.
Is it such a stretch to think they could also treat neurological disorders?
Perhaps — at least when it comes to Alzheimer’s disease.
This month, scientists from Novo Nordisk, the company that makes Ozempic, presented data at an Alzheimer’s research conference showing that the compound in the drug had failed to slow the progression of early Alzheimer’s in two clinical trials.
To some researchers, the results are a reason to temper enthusiasm around this class of medication and its potential to treat some brain-related conditions.
“It’s a little bit sobering, and we have to tone down the ‘wonder drug’ discussion and be very realistic,” said Daniel Drucker, a researcher at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto and one of the first scientists to study medications like Ozempic. (Dr. Drucker has consulted for Novo Nordisk.)
Others remain optimistic that the medications hold potential.
“It was very disappointing, let’s put it that way, in terms of what we were anticipating,” said Dr. Paul Edison, a professor of neuroscience at Imperial College London, who led another study testing a similar drug to treat Alzheimer’s and has also consulted for Novo Nordisk.
But, he added, “the fundamental theory is still quite sound.”
Why were scientists hopeful that a diabetes drug could treat dementia?
Medications like Ozempic mimic a naturally occurring hormone called glucagon-like peptide-1, or GLP-1, which helps regulate blood sugar and appetite. GLP-1 is primarily secreted from the intestines, but the brain also produces some of the hormone.
Scientists have long known that GLP-1 and other gut hormones have “positive effects on cognition,” said Dr. William Banks, a professor of gerontology and geriatric medicine at the University of Washington who has been studying the hormone for decades.
GLP-1 medications cause weight loss in part because they act on areas of the brain related to reward and satiety. Some are also able to cross the blood-brain barrier, reaching parts of the brain that play an important role in memory.
These drugs may affect brain health indirectly, too. One of the prevailing theories is that they tamp down inflammation throughout the body, including in the brain, and that could help lower the risk for dementia.
Research in mice has underscored the drugs’ potential benefits, finding that GLP-1 medications can prevent, or even reverse, cognitive impairment and signs of Alzheimer’s disease in the animals, including the accumulation of the protein tau, a hallmark of the condition. However, there is a long history of drugs successfully treating dementia in rodents but failing to do so in humans.
Early research on people was promising. Results from several epidemiological studies found that people with Type 2 diabetes who took Ozempic or similar drugs had a lower risk of developing dementia than those on other types of diabetes medications. And in a small clinical trial led by Dr. Edison, another GLP-1 drug slightly slowed cognitive decline in people with mild to moderate Alzheimer’s disease.
So why did the new trials fail?
The two clinical trials included roughly 3,800 people who were diagnosed with either mild cognitive impairment or early dementia and had signs of amyloid plaques in their brains, another hallmark of Alzheimer’s. Half of the participants took a pill form of semaglutide, the substance in Ozempic, and the other half took a placebo.
The researchers hoped that, over the course of two years, the patients taking semaglutide wouldn’t experience as much cognitive decline as those taking a placebo, and maybe they wouldn’t progress from one stage of dementia to the next. But in the data presented at the Alzheimer’s conference there was no difference between the two groups.
The researchers also looked at biomarkers in the patients’ blood and spinal fluid, and did note some differences: The participants who received semaglutide showed a decrease in both tau and inflammation. But that decrease was probably too small to have “the corresponding benefit on the cognition that we had hoped for,” Dr. Jeffrey Cummings, a professor of brain science at the University of Nevada, Las Vegas, said during the conference presentation.
Scientists don’t know for certain why the trials failed, but they have a few guesses. The main one is that the medication wasn’t very effective at getting into the participants’ brains. That could be because the semaglutide molecule was too big to deeply penetrate the blood-brain barrier (earlier studies in mice, as well as Dr. Edison’s trial, used an older GLP-1 medication made of smaller molecules).
“These agents were developed for Type 2 diabetes,” said Nigel Greig, a senior investigator at the National Institutes of Health who has studied these drugs for neurodegenerative disorders. “It’s a systematic disorder. So they really weren’t designed to go into the brain.”
Or it could be that the pill form of the medication was less effective because not as much of the drug enters the bloodstream when it is taken orally, compared with an injectable version.
“How much, actually, it gets into the brain is quite debatable,” Dr. Edison said. “That may very well be one of the reasons why it didn’t work.”
Scientists understand nearly nothing about how the pill formulation of semaglutide might be able to access the brain, said Karolina Skibicka, a neuroscientist at the Hotchkiss Brain Institute at the University of Calgary. That’s a big reason “why I wouldn’t necessarily expect miracles out of this treatment,” she said.
It’s also possible that this class of medication could still work as a form of prevention for dementia, but not as a treatment, Dr. Edison said.
“They’re going to be very effective drugs for certain types of things, and we have to learn what those are and maximize the opportunities,” Dr. Greig said.
But, he cautioned: “There are no drugs for everything.”
Dana G. Smith is a Times reporter covering personal health, particularly aging and brain health.
The post In New Dementia Trials, Ozempic’s ‘Miracle Drug’ Image Takes a Hit appeared first on New York Times.
