Hopes were high. In retrospect, perhaps too high.
On Monday, Novo Nordisk announced that two large studies failed to find any effect of the drug semaglutide on cognition and functioning in people with mild cognitive impairment — an early stage of Alzheimer’s — or with dementia. The participants were randomly assigned to take a pill of semaglutide, the compound at the heart of the weight-loss injections Ozempic and Wegovy, or a placebo for two years.
“Today we announced that our efforts to slow down the progression of Alzheimer’s disease has come to an end,” said Maziar Mike Doustdar, chief executive at Novo Nordisk, in a video posted on LinkedIn.
He added, “Based on the indicative data points we had, this is not the outcome we had hoped for.”
The studies, involving 1,855 people in one trial and 1,953 in the other, seemed to stem an initial phase of optimism. The drugs appeared miraculous in their treatment of obesity, diabetes, heart disease and kidney disease. Alzheimer’s and other brain illnesses looked like the next frontier.
But there had been other recent warnings, in two smaller studies of brain diseases. One, done by researchers in Britain, asked if a similar drug could help with Parkinson’s disease. That drug had no effect.
Another study found that semaglutide did not help with cognitive impairment in people with major depression, a severe form of the disease.
The company will present more detailed results from its Alzheimer’s study at a conference on Dec. 3, and another in March of 2026.
Novo Nordisk’s stock was down nearly 6 percent on Monday, deepening a monthslong slump for the once-surging company.
“We always knew there would be a low likelihood of success, but it was important to determine if semaglutide could take on one of medicine’s most challenging frontiers,” Mr. Doustdar said.
Some Alzheimer’s specialists, like Dr. John C. Morris, a professor of neurology at Washington University in St. Louis, said that from the start they had not been optimistic that semaglutide would work in Alzheimer’s.
He and others wondered: Why might it work? A starting hypothesis was that the drugs might reduce inflammation, which occurs in Alzheimer’s disease.
“There is no question that neuroinflammation is deleterious,” Dr. Morris said. Yet, he noted, it might be difficult to quell it in Alzheimer’s. A quarter century ago, researchers had tried giving anti-inflammatory drugs to patients with Alzheimer’s and they did not help, Dr. Morris said.
The only way to really know was to perform the research Novo Nordisk did, in a placebo- controlled study.
In explaining why it had tested the hypothesis, the company pointed to “real-world evidence studies, preclinical models, as well as post-hoc analysis from diabetes and obesity trials.”
It did not cite specific studies. But among the real-world evidence studies is one that examined the electronic health records of 116 million patients. It found that those who were taking semaglutide for diabetes were 40 to 70 percent less likely to be diagnosed with Alzheimer’s than those taking other diabetes medications.
Another such study, involving Veterans Affairs records for patients with diabetes, found that semaglutide seemed to help with a wide variety of disorders, including brain-related conditions.
For some researchers, there was a lesson here about how doctors and the general public sometimes seize upon studies that generate a hypothesis, then assume that they are offering proof.
In the case of the studies of people taking semaglutide for diabetes, those subjects are likely to have been different from those taking other diabetes drugs. Investigators try to control for such differences, but they can control only for the ones they know. The annals of medicine are replete with observational studies that seemed to prove a treatment was effective, only to have it fail in more rigorous studies.
The research was also motivated by studies with mice. One study in mice with an Alzheimer’s -like disease found that semaglutide could improve memory and even increase the number of neurons in the mice that were part of the study.
But mice do not naturally get Alzheimer’s, so the study is in effect an artificial construct.
The results from study after study, all pointing to hope for semaglutide and Alzheimer’s, were what might now appear to be irrational exuberance.
But some Alzheimer’s experts retain a glimmer of hope.
Dr. Eric Reiman, chief executive of the Banner Alzheimer’s Institute in Phoenix, said it remains possible that semaglutide might help people who are at risk, but have not yet developed dementia. He’s waiting to see the details of the Novo Nordisk study that the company will present at a meeting next week, hoping for a sign that the drug could be effective if introduced earlier.
The current study, he said, “might be too little, too late.”
Rebecca Robbins contributed reporting.
Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.
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