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Medical experts are warning that Wegovy and similar fat-loss shots may cause a potentially deadly side effect overlooked in trials.
The blockbuster drugs work by mimicking the effects of GLP-1, a hormone that slows the movement of food through the intestines – making a person feel full for longer.
But researchers in China believe the drugs may cause a person’s small intestine to become enlarged, which puts them at high risk of a potentially deadly obstruction in their digestive system.
In experiments performed on mice, the enlargement of the intestine occurred at around 20 months of taking GLP-1 drugs. The team points out that clinical trials for Wegovy, which has a sticker price of over $1,000 per month, only went up to 16 months, meaning this significant long-term side-effect may have been missed.
Wegovy, developed by the Danish Novo Nordisk, is a weekly injectable drug that leads to heavy weight loss long term (file photo)
Chinese researchers warn that people who take GLP-1 drugs such as Wegovy will experience an enlarged intestine, which is less flexible and more prone to blockages
The drug has seen uptake among Hollywood’s biggest stars. Actress Chelsea Handler, 48, admitted to using the drug – though unknowingly – to lose weight earlier this year
The researchers also reviewed previous research on humans that suggest users of these types of drugs are up to four times more likely to suffer intestinal obstruction.
‘Because [this class of drugs] could cause continuous increases in the intestinal length and villus height, the small intestine may become as inelastic… leading to long-term upper intestinal obstruction,’ the scientists wrote.
Intestinal obstructions occur when a blockage prevents food and liquid from passing through the intestines. This can be caused by damage to the digestive system, cancer, or an inflamed or stretched intestine.
One of the earliest signs someone is suffering a blockage is a loss of appetite and constipation.
The blockage can occur when an intestine becomes too large, as it loses the ability to adjust its shape – making it difficult for food to pass through.
If left untreated, intestinal obstruction can cause serious, life-threatening complications, including tissue death.
The condition can cut off the blood supply to part of your intestine, with the lack of blood causing the intestinal wall to die.
Sufferers are also at a higher risk of peritonitis, a potentially deadly infection within the abdomen.
Intestinal obstruction is responsible for around 30,000 deaths in the US every year.
Elon Musk (left) credits his spectacular weight loss in 2020 to Wegovy. The tech tycoon looked noticeably slim when he first arrived in Twitter HQ after purchasing the company in October (right)
A UK study found that people who used Wegovy experienced rapid weight loss, dropping 18% of their weight over 68 weeks. They regained two-thirds of that weight, or 12% of their original body weight in the year after dropping the weekly injections. Experts says the drug needs to be used over a lifetime to keep off the pounds
But independent experts not involved with the research told DailyMail.com that the medication should be safe for most and encouraged doctors to look at patients’ history of bowel problems before prescribing.
But it is the latest potential side effect to emerge. Last month doctors told DailyMail.com that most patients lose more muscle than fat while taking the drug.
And trials show that patients who come off the drug pile the pounds back on in months.
Despite the concerns, Wegovy, its sister drug Ozempic, and other similar weight loss drugs were instant hits in the pharmaceutical industry, becoming so popular they spent much of last year in short supply. Novo Nordisk, its manufacturer, says supply issues will soon be quelled.
The Chinese team, who published their report last month in Acta Pharmaceutica Sinica B, a leading pharmacology journal in the Asian nation, highlighted dangers found in previous research. They cited two studies that show a correlation between the drugs and stomach issues.
One study, published by French researchers at the end of 2020, used data from VigiBase, the World Health Organization’s tracker for global adverse drug reactions.
After observing over 500,000 reports, they found that people who used GLP-1 drugs for diabetes management were 4.5 times more likely to suffer intestine obstruction.
While Wegovy did not become available globally until 2021 – after this study – its sister drug, Ozempic, which uses the same active ingredient, was rolled out in 2017.
Wegovy causes users to lose their muscle mass, doctors say
The medications have been touted as wonder drugs after initial clinical trials.
In a 2022 study, British researchers compared rates of intestinal obstructions between 25,617 GLP-1 users and 67,261 users of another type of diabetes drug.
They found that GLP-1 users suffered a 3.5 fold risk of intestine obstruction.
Both of these studies were observational and established a correlation between GLP-1 use and stomach issues – but could not confirm they were directly related.
Intestinal obstruction is a known symptom of diabetes too, meaning the study could just be finding proof of that symptom at a large scale.
‘It is very difficult to tell if the obstruction is a direct result of the medication,’ Dr Shauna Levy, an obesity medicine specialist at Tulane University who was not involved with the latest study, told DailyMail.com.
‘Physicians should consider a patient’s history of bowel obstruction before prescribing this medication.
‘This does highlight an important point that GLP-1 RA are medicine. They should be prescribed by a health care provider who can screen the patient beforehand for a history of contraindications to the medication.’
She cited a 2022 study conducted by scientists from across the globe – including the University of Alabama, Birmingham and the University of Pennsylvania.
This research followed semaglutide users for two years, and found no increased risk of intestine obstruction among this population.
Dr Christopher McGowan, a weightloss specialist in North Carolina, agreed.
He told DailyMail.com: ‘While this discussion raises possible concern, it is difficult to extrapolate these findings to conclude any potential impact on humans.
‘While the clinical studies of GLP1 medications are indeed of relatively short term (less than 2 years duration), the GLP1 medications as a whole have been in use and studied for more than a decade, which provides general reassurance.
‘However, the introduction of the newer GLP1 medications, such as semaglutide, to a much wider population (on the order of many millions of persons) may expose less common adverse events. This necessitates very close monitoring and reporting. Considering that these medications are designed to be long-term, chronic treatments, there is still much to be learned regarding their cumulative risk after multiple years of use.’
But, the Chinese team cites previous research in mice to make their case.
A 2007 study by Danish researchers found that rodents who had been exposed to the drugs had the length of their small intestines grow nine percent and the width 31 percent.
Dr Christopher McGowan (left), a weightloss specialist in North Carolina, told DailyMail.com that there is already long term data supporting the use of GLP-1 drugs, but these findings should be considered by doctors before prescribing it. Dr Shauna Levy (right), a weightloss specialist at Tulane University, told DailyMail.com that other studies found that GLP-1s are safe after using for two years
Interestingly, Dr Lotte Simonsen, who led that research, would begin work in obesity research for Novo Nordisk in 2010 – a few years after that study. She holds the role of ‘Scientific Director’ at Wegovy’s manufacturer, according to her LinkedIn page.
A German study from last year found that GLP-1 drugs increased the length of bowels by 20 percent and the height of the small intestine 34 percent.
These studies used exenatide and dapiglutide for their research. While both are GLP-1s, they are different from the semiglutide used in Wegovy.
Dr Levy said that the findings in mice may not have much bearing on human outcomes, though.
‘Also animal studies should be seen more as hypothesis-generating, rather than proof of outcome in humans,’ she explained.
Chinese scientists still note the concerns, though. And, they point to the way the drugs are used for these issues.
Users of drugs such as Wegovy and Ozempic self-administer a once-weekly injection of the medication.
Doses start small, at 0.25mg, before working their way up to the 2.4mg per week maintenance phase.
The body does not naturally produce GLP-1 hormones like this. Instead, it produces them when needed to regulate appetite. Naturally, there will never be that level of hormones active in the body at once.
Semgalutide also has a half-life of around seven days, meaning when a person takes their weekly injection, much of last week’s injection is still in their body.
The Chinese team is not certain, but they fear this could cause issues for a person’s digestive system.
The scientists say it is hard to measure the growth of a person’s intestine, meaning it is unlikely that it would have been caught in clinical trials.
The earliest sign of the stomach issue is constipation, a frequent symptom that a multitude of other health issues could cause.
Wegovy has been a golden goose for the Danish Novo Nordisk since it first became available in 2021.
In clinical trials, obese people who used the drug alongside a fitness plan dropped 15 percent on their body weight over 68 weeks – far outpacing other weight-loss drugs.
The drug, a reformulated version of its diabetes drug Ozempic, was so popular that its stock was nearly wiped out for the second half of 2022.
It comes with a high price, too, costing users over $1,000 per month if their insurance does not pay for it.
Concerns are rising about its use, though. Some fear that doctors are now turning towards pharmaceuticals to fix America’s growing obesity crisis – instead of the more natural diet and exercise.
Another study also found that users of the drug will regain all of their lost weight once the drop the weekly shots.
‘GLP-1 receptor agonists (GLP-1 RAs) have been used to treat type 2 diabetes (T2D) for more than 15 years, including Novo Nordisk products that have been on the market for more than 10 years,’ a Novo Nordisk spokesperson told DailyMail.com.
‘Semaglutide has been extensively examined in robust clinical development programmes, large real-world evidence studies and has cumulatively more than 9.5 million patient years of exposure.
‘Gastrointestinal side effects are well-known side effects of the GLP-1 RA class. The majority are of mild to moderate severity and of short duration. Patient safety is of utmost importance to Novo Nordisk and we are continuously collecting safety data on our marketed GLP-1 RAs and collaborating closely with authorities to ensure patient safety.
‘Over 25,000 participants have been exposed to semaglutide injection T2D (Ozempic®), oral semaglutide for T2D (Rybelsus®) or semaglutide injection for weight management and obesity (Wegovy ®) in completed clinical studies conducted by Novo Nordisk (up to 2.5 years of study duration).
‘Furthermore, more than 30,000 patients are currently being evaluated in ongoing long term clinical studies with semaglutide. Novo Nordisk evaluates that the benefit- risk profile of its marketed GLP-1 receptor agonist products continues to remain favourable.’
The drug has seen uptake among Hollywood’s biggest stars. Actress Chelsea Handler admitted to using the drug – though unknowingly – to lose weight earlier this year.
Billionaire tech tycoon Elon Musk has admitted to using Wegovy for weight loss on his Twitter last year.