CNN
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New analyzes of the longest clinical trial to date of the weight-loss drug Wegovy are illustrating how quickly it helps people lose weight, how long they sustain that weight loss, and how safe the drug is over four years of use.
Analyzes of a trial called Select, the results of which last year showed that Wegovy significantly reduced heart risk in addition to helping with weight loss, also suggest that the drug may protect the heart in ways beyond weight loss, the researchers said, raising new questions about how the wildly popular drugs in this drug class should be used and covered by insurers.
The implications are profound, said Dr. Harlan Krumholz, a cardiologist and scientist at Yale University and Yale New Haven Hospital who was not involved in the research. noting that a second study this week showed a similar finding for heart failure. We have not found any drug with such a wide range of benefits for the heart.
More than 25,000 people in the US are starting Wegovy every week, drugmaker Novo Nordisk said this month. And in a KFF survey released Friday, 6 percent of respondents said they were currently using a drug 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 how widely and how long they have been studied. The Select trial, which was funded by Novo Nordisk, showed last year that Wegovy reduced the risk of heart attack, stroke or heart-related death by 20% in people at existing cardiovascular risk with obesity or overweight It included more than 17,600 people from 41 countries between 2018 and 2021 and followed them for several years.
Researchers have continued to explore the data, and the new analysis, presented Monday at the European Congress on Obesity and published in the journal Nature Medicine, shows results for people taking Wegovy for up to four years. Here are some of the main takeaways:
The analysis showed an average weight loss of just over 10% for people who used semaglutide, the active ingredient in Wegovy, compared to 1.5% of study participants who received a placebo. The researchers, led by Dr. Donna Ryan of the Pennington Biomedical Research Center in Baton Rouge, Louisiana, noted that the trend showed that participants taking the drug typically lost weight for about 65 weeks, or one year and three months, before ‘reach a plateau.
An earlier clinical trial showed an even greater average weight loss for Wegovy: about 15% on average over 68 weeks, compared with 2.4% for people who received a 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 interventions on style of life on diet and exercise compared to the Select trial, which was designed to test whether the drug prevented heart events.
The results showed that the average weight loss of 10% for people using Wegovy was maintained for up to 208 weeks, or four years.
Patients stayed on the medication as long as they maintained their weight loss. Other studies have shown that many people regain weight after stopping the drugs, including one published in December by Novo Nordisk competitor Eli Lilly: People using the GLP-1 drug Zepbound, which uses the active ingredient tirzepatide and targeting a second hormone called GIP, they lost an average of 21% of their body weight over 36 weeks. The participants were then split into two groups, with those who stayed with the drug losing an additional 5.5 percent of their body weight, while those who unknowingly switched to a placebo gained back 14 % of its weight.
However, not everyone recovered as much weight The study also looked at how many people maintained at least 80 percent of their weight loss after the initial 36 weeks, and while many more who continued to take the drug did nearly 90 percent, nearly 17 percent of people who switched to a placebo maintained that much weight loss without the drug.
In the new analysis, researchers reported that after two years, about 68% of people taking Wegovy had lost at least 5% of their body weight, compared to 21% of people taking a placebo. Almost 23% of people on Wegovy lost at least 15% of their body weight, compared with 1.7% on a placebo. And nearly 5 percent of people who took the drug lost more than 25 percent of their body weight, compared with 0.1 percent on the placebo, showing that the main results of the studies are only averages; everyone has a different experience with medications.
Overall, more people in Wegovy decided to stop participating in the trial because of side effects than people who received a placebo: 17% of those who took the drug compared with 8% on the placebo, a result that was reported earlier. And the side effects were those that are widely known with these drugs: mainly gastrointestinal disturbances such as nausea, diarrhea, vomiting and constipation, which commonly affected people in the first months of the study as the dose of the drug was increased.
The researchers noted that no new safety signals were seen in the latest analyses. Acute pancreatitis, or inflammation of the pancreas, was not seen at a higher rate among patients on Wegovy than on placebo, although gallbladder disorders such as gallstones were: 2.8% for people with Wegovy, compared to 2.3% for people on placebo. Both are included in warnings in the drug’s prescribing information because they had previously been seen in trials.
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’s something more at play.
That’s because the reduction in risk of heart attack or other events was seen even in people using Wegovy who didn’t lose weight.
You probably don’t even need to lose weight to get the cardiovascular benefit from semaglutide and similar drugs, 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 you have diabetes or not, regardless of whether you’re obese and you don’t need to lose weight, it’s not the whole story.
An analysis led by John Deanfield of University College London found that the reduction in major adverse cardiovascular events in the study for Wegovy patients, compared with placebo, was similar among people who lost 5% or more of their body weight and those who lost the least. than that or even those who gained weight.
This suggests alternative mechanisms for improving cardiovascular outcome beyond reducing adiposity or body fat, the researchers concluded.
A separate study published Monday on heart failure, by that Wegovy has shown a significant benefit suggested the same, Krumholz said.
These two studies show that these anti-obesity drugs are also heart-healthy drugs, he wrote in an email. The heart benefits for people with established cardiovascular disease or a certain type of heart failure occur regardless of the amount of weight loss.
Drucker suspects that GLP-1 drugs provide these kinds of benefits by reducing inflammation.
We can’t ignore lowering blood pressure or lowering triglycerides, and lowering body weight has to help a little bit, and glucose has to help a little bit, he said.
But based on his lab research, he said, one of my favorite theories is inflammation, because we know that people with cardiovascular disease do have increased inflammation in their blood vessels and heart.
Drucker said studies have shown that GLP-1 drugs reduce harmful inflammation, which his lab is studying. He even noted that he receives communications from people with conditions like Covid-related brain fog, ulcerative colitis and inflammation-driven arthritis who believe their symptoms have improved while using GLP-1 drugs. These links would need to be confirmed in clinical studies to be considered definitive.
The results of the Select trial, he said, raise the question of whether people who are not obese or overweight but have had a heart attack or stroke might benefit from taking a drug like Wegovy to prevent another event another thing that should be studied.
And, Drucker said, the results suggest that insurers should cover the drugs, which cost about $1,000 a month or more without them, more widely.
We probably need to rethink these criteria for reimbursing drugs, because they will be useful in improving health and saving lives and saving money in health care in people with obesity and heart disease, even without losing too much weight, he said. You don’t even need to lose weight to reduce heart attack, stroke and death.
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