nytimes.com
Wegovy, the popular obesity drug, may have yet another surprising benefit. In a large clinical trial, people taking the drug during the pandemic were less likely to die of Covid-19, researchers reported on Friday.
People on Wegovy still got Covid, and at the same rate as people randomly assigned to take a placebo. But their chances of dying from the infection plunged by 33 percent, the study found. And the protective effect occurred immediately — before participants had lost significant amounts of weight.
In addition, the death rate from all causes was lower among subjects taking Wegovy, a very rare finding in clinical trials of new treatments. The result suggests that lower life expectancy among people with obesity is actually caused by the disease itself, and that it can be improved by treating obesity.
“Stunning,” Dr. Jeremy Faust, an emergency room physician at Brigham and Women’s Hospital who wrote an editorial accompanying the study, said of the data. The study was published in The Journal of the American College of Cardiology.
The study was not originally designed to look at the effects of taking Wegovy on people with Covid. But the participants taking the drug were not healthier than the others, said Dr. Harlan Krumholz, a cardiologist at Yale and the editor in chief of the journal.
“It is a randomized trial and the infection rates were similar, so this represents top-notch evidence,” he said.
The discovery arose after investigators seized an unprecedented opportunity to ask a question they had never foreseen, said Dr. Benjamin Scirica, a trial investigator who is a cardiologist and senior physician at Brigham and Women’s Hospital.
Would Wegovy have any effect on Covid infections? “I don’t think any of us anticipated there would be a drug effect,” he said.
As the Covid epidemic erupted, a large clinical trial of Wegovy, sponsored by its maker, Novo Nordisk, was already underway. The goal was to learn whether the drug prevented deaths from heart disease and health events like heart attacks.
The study’s 17,604 participants had heart disease and an average body mass index of 27 or higher. They did not have diabetes. They were followed for more than three years.
But the pandemic complicated things. The trial participants were among those most likely to die or become very ill from Covid, as they had both obesity and heart disease.
The first challenge was just to keep the study going in a time of lockdowns and social distancing. “We had to make dramatic changes to make sure the study would continue and that the subjects would continue to get their medications,” Dr. Scirica said.
Some study investigators would drive to a meeting place, drop off a bag of medications and walk away to watch while a participant arrived to pick it up, in order to make it a touchless encounter.
The researchers changed their data collection forms to record Covid infections and, when vaccines became available, immunizations. They began noting whether a death was related to Covid.
A total of 4,258 participants became infected with Covid, nearly equally divided between those taking Wegovy and those taking a placebo. Of those patients, 184 died — 78 of those who had been assigned to take Wegovy and 106 taking a placebo, a significant difference.
The obesity drug also reduced the overall death rate by 19 percent, the researchers reported. Although it was known that people with obesity have shortened life spans, this is the first rigorous study to show that treating obesity itself helps people live longer.
“Most of our studies in the cardiovascular world — with statins or other cardiovascular drugs — have a pretty good effect on cardiovascular deaths but don’t affect non-cardiovascular deaths,” he said. These included huge studies with hundreds of thousands of patients.
Dr. Faust said he was shocked by the effect on mortality overall. “All the hype around various pharmaceutical drugs that we hear is exactly that — hype,” he said. “But these drugs are repeatedly and routinely demonstrating that they are game changers.”
Because the patients had a median age of 61, the decrease in deaths from all causes “means that even if 30 years from now there turns out to be some risks that we don’t yet know about, those would have a steep climb to overcome the benefits around saving years or decades of life,” Dr. Faust added.
The class of drugs that includes Wegovy, he noted, has been studied in patients for 10 to 15 years, “so it’s not like this is some therapy we’ve had for a year or two.”
But why do Wegovy and other so-called GLP-1 agonists have these effects? “It’s something more than just losing weight,” said Dr. David Maron, a cardiologist at Stanford and director of the Stanford Prevention Research Center.
Dr. Faust suggests that the drugs are improving overall health, including reducing chronic inflammation.
When a young and healthy person gets the flu, he said, “it will cost a week of work and misery.” But the situation is different if the person is in a nursing home. Then that flu infection can be fatal. Organs may fail as the body shifts resources to fight the infection.
Might Wegovy and drugs like it also protect people from dying from other infectious diseases, like flu or R.S.V.? Dr. Faust and Dr. Maron now think it’s possible.
Dr. Scirica wants to go back and look at other studies of GLP-1 drugs to see if they had an effect on infectious diseases. And he said that in new studies, researchers should deliberately plan to look for such data.
Given what has been discovered so far in studies with the new obesity drugs, “I expect to be surprised,” said Jon Zelner, an infectious disease epidemiologist at the University of Michigan.