New analyzes from the longest-ever clinical trial of the weight-loss drug Wegovy are shedding light on how quickly it helps people lose weight, how long they sustain that weight loss, and how safe the drug is after four years of trial. use.
The analyzes – from a test called Select, whose results showed last year that Wegovy significantly reduced heart risk in addition to helping with weight loss — it also suggests that the drug may protect the heart in ways that go beyond weight loss alone, researchers said, raising new questions about how Extremely popular drugs in this drug class should be used – and covered by insurers.
“The implications are profound,” he said. Dr. Harlan Krumholza cardiologist and scientist at Yale University and Yale New Haven Hospital who was not involved in the research, noting that a second to study this week showed a similar finding for heart failure. “We haven’t found a medicine with so many benefits for the heart.”
More than 25,000 people in the US are starting Wegovy every week, says drugmaker Novo Nordisk he said this month. And in a KFF survey released on Friday, 6% of respondents said they were currently using a medication in this class, known as GLP-1 receptor agonists. That translates to more than 15 million Americans.
An important question about these blockbuster drugs is to what extent – and for how long – they have been studied. The Select trial, funded by Novo Nordisk, showed Last year, Wegovy reduced the risk of heart attack, stroke or heart-related death by 20% in people with existing cardiovascular risk, obesity or being overweight. It included more than 17,600 people from 41 countries between 2018 and 2021 and followed them for several years.
Researchers continued to explore the data and new analyses, presented Monday at European Congress on Obesity and published in the magazine Nature Medicine, show results for people who take Wegovy for up to four years. Here are some important lessons:
Weight loss continued for over a year
The analysis showed an average weight loss of just over 10% for people who used semaglutide, the active ingredient in Wegovy, compared with 1.5% for study participants who received a placebo. Donna Ryan of the Pennington Biomedical Research Center in Baton Rouge, Louisiana, noted that the trend showed that participants taking the medication typically lost weight for about 65 weeks, or a year and three months, before hitting a plateau.
A previous clinical trial showed even greater average weight loss for Wegovy: about 15% on average over 68 weeks, compared with 2.4% for people who received placebo. Researchers in the new analysis noted that, in addition to some differences in the people who enrolled in each trial, the previous study was designed specifically for weight loss and included more structured lifestyle interventions around diet and exercise compared to the Select trial. , which was designed to test whether the drug prevented cardiac events.
It was sustained for up to four years
Results showed that the average 10% weight loss for people who used Wegovy was sustained for up to 208 weeks, or four years.
Patients remained on the medication while maintaining weight loss. Other studies have shown that many people regain weight after stopping medications, including one Published in December from Novo Nordisk competitor Eli Lilly: People using the GLP-1 drug Zepbound, which uses the active ingredient tirzepatide and targets a second hormone called GIP, lost an average of 21% of their body weight in 36 weeks. Participants were then divided into two groups, and those who continued taking the drug lost an additional 5.5% of their body weight, while those who unknowingly switched to a placebo gained 14% of their weight back.
However, not everyone has regained that much weight. The study also looked at how many people maintained at least 80% of their weight loss after the initial 36 weeks, and while many others who continued the drug did so – nearly 90% – almost 17% of people who switched to a placebo maintained as much weight loss. weight without the drug.
Results vary for everyone
In the new analysis, researchers reported that after two years, about 68% of people who took Wegovy lost at least 5% of their body weight, while 21% of people who took placebo did. Nearly 23% of people who took Wegovy lost at least 15% of their body weight, compared to 1.7% who took a placebo. And almost 5% of people who took the drug lost more than 25% of their body weight, compared to 0.1% who took the placebo, showing that the studies’ main conclusions are just averages; Everyone has a different experience with medications.
No security surprises in four years
Overall, more people who took Wegovy decided to stop participating in the study because of side effects than people who took a placebo: 17% of people who took the drug versus 8% who took a placebo, a result that was previously reported. And the side effects were widely known with these drugs: mainly gastrointestinal disorders like nausea, diarrhea, vomiting and constipation, which generally affected people in the first few months of the study as the dose of the drug increased.
The researchers noted that there were no new safety signals observed in the latest analyses. Acute pancreatitis, or inflammation of the pancreas, was not seen at a higher rate among those taking Wegovy than placebo, although gallbladder disorders such as gallstones were: 2.8% for people taking Wegovy , compared with 2.3% for people who received a placebo. Both are included in warnings on the medicine prescribing information because they were previously seen in testing.
Benefits beyond weight loss
A key question when the full results of the Select trial were initially presented was whether the 20% reduction in heart risk was driven by weight loss alone or some other protective effect of the drug. The new analysis suggests there is something more at play.
This is because the reduced risk of heart attack or other events was seen even in people who used Wegovy and who did not lose weight.
“You probably don’t even need to lose weight to get cardiovascular benefits” from semaglutide and similar medications, said Dr. Daniel Drucker, a pioneer of GLP-1 research at the University of Toronto who was not involved in the new analyses. “That’s because that’s what GLP-1 does: it’s cardioprotective, at least in animals, regardless of whether or not you have diabetes, regardless of whether you have obesity, and it doesn’t require weight loss – that’s not all. .”
One analysis led by John Deanfield from University College London found that the reduction in major adverse cardiovascular events in the study for those taking Wegovy, compared with placebo, was similar between people who lost 5% or more of their body weight and those who lost less than that or even those who have gained weight.
“This suggests alternative mechanisms for improving cardiovascular outcomes in addition to reducing adiposity” or body fat, the researchers concluded.
A separate study published Monday about heart failure, for which Wegovy showing a great benefit, suggested the same thing, Krumholz said.
“These two studies show that these anti-obesity drugs are also heart health drugs,” he wrote in an email. “The benefits to the heart of people with established cardiovascular disease or a certain type of heart failure occur regardless of the amount of weight loss.”
A benefit of reducing inflammation
Drucker suspects that GLP-1 drugs provide these types of benefits by reducing inflammation.
“We can’t ignore lowering blood pressure or lowering triglycerides, and lowering body weight should help a little, and glucose should help a little too,” he said.
But based on his laboratory research, he said, “one of my favorite theories is inflammation, because we know that people with cardiovascular disease have increased inflammation in their blood vessels and heart.”
Drucker said studies have shown that GLP-1 drugs suppress harmful inflammation, which his lab is studying. He even noted that he receives communications from people with conditions such as Covid-related brain fog, ulcerative colitis and arthritis – caused by inflammation – who feel their symptoms have improved with the use of GLP-1 medications. These links would need to be confirmed in clinical studies to be considered definitive.
The Select trial results, he said, raise the question of whether people who are not obese or overweight, but who have had a heart attack or stroke, could benefit from taking a drug like Wegovy to prevent another event – another event. something that would need to be studied.
And, Drucker said, the results suggest that insurers should cover the drugs, which cost about a thousand dollars a month or more without them, more broadly.
“We probably really need to rethink these criteria for reimbursing drugs because they’re not going to be helpful in terms of actually improving health and saving lives and saving health care dollars,” he said. “You don’t even need to lose weight to reduce heart attacks, strokes and deaths.”
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