“Anyone who has tried to lose weight through diet and exercise will appreciate how difficult it is, so the introduction of a safe and effective drug will of course be in demand.” Photo / Getty Images
“Anyone who has tried to lose weight through diet and exercise will appreciate how difficult it is, so the introduction of a safe and effective drug will of course be in demand.” Photo / Getty Images
There has been meteoric demand for the weight-loss drug Wegovy since it was approved in Britain 11 months ago, fuelled by eye-popping trial results that revealed obese patients lost an average of 15 kilograms in a year – equivalent to one-and-a-half car tyres of fat. Backing from famous faces only increased the appetite for the medication, which scientists have compared to the furore around Viagra when it was approved in the late 1990s.
“I cannot think of another condition as widespread as obesity that is so intimately associated with body image and self-esteem as well as health,” says Dr Simon Cork, a senior lecturer in physiology at Anglia Ruskin University in England. “Anyone who has tried to lose weight through diet and exercise will appreciate how difficult it is, so the introduction of a safe and effective drug will of course be in demand.”
However, as with any new drug, scientists are still learning about it. As well as triggering weight loss – a result of the active ingredient semaglutide making users feel full – studies have also linked the drug with a myriad of side effects, good and bad. Dramatic drops in the risk of cancer and heart problems have been reported but so have digestive problems and blindness.
Then there’s the fact many people are purchasing what they believe to be semaglutide from unregulated sellers online, which puts them at risk of a host of other complications, including hospitalisation. All of which makes it even more important to go via a qualified healthcare provider if you believe your health could benefit from taking them.
“We don’t yet have 10-year data on the effect of high doses, so continued vigilance is needed,” says Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow in Scotland. “But so far, most researchers are reassured as are regulators in the UK, United States and Europe.” Sattar and Cork have unpacked the side effects to be aware of.
Blindness
Doctors at Massachusetts Eye and Ear hospital in Boston, US, began probing whether there was a link between weight-loss jabs and blindness after seeing three patients in the space of the week, all of whom were taking Ozempic or Wegovy and had developed a rare sight-loss condition.
Both drugs contain semaglutide at different concentrations. Ozempic is only licensed for Type 2 diabetes patients in Britain (though some doctors prescribe it off-label for weight loss), while Wegovy has been approved to help overweight and obese patients shift the scales.
Doctors looked back through six years of data relating to almost 17,000 patients.
They found people with Type 2 diabetes taking semaglutide were at least four times more likely to be diagnosed with nonarteritic anterior ischemic optic neuropathy (NAION). People who were overweight or obese taking the drug were more than seven times as likely to develop it.
NAION is uncommon but affects one in 10,000 people and causes sudden, irreversible blindness. It occurs from a lack of sufficient blood flow to the optic nerve and people typically suffer sudden vision loss in one eye, without any pain, and often on waking up. There is no treatment for the condition and vision often does not improve.
There is only one paper reporting a link between NAION and semaglutide and it is observational – meaning it can’t prove the drug was to blame, notes Sattar. “There is a need for better data in this space before any conclusions can be drawn. This is not saying there is not a risk. We simply don’t know and better data is needed before any conclusions can be drawn.”
The majority of people who take semaglutide experience some gastrointestinal side effects, at least transiently. Photo / 123rf
Stomach problems
Trials of semaglutide revealed that gastrointestinal discomfort – nausea, diarrhoea, vomiting and constipation – were a common side effect of the drug, affecting three-quarters of participants given a weekly 2.4mg dose (the maintenance dose for Wegovy).
Researchers noted stomach problems were not usually severe but admitted 7% of the group left the trial, in most cases because of stomach problems.
“The majority of people who take semaglutide experience some gastrointestinal side effects, at least transiently,” says Cork. “These tend to be mild, but can in some cases be significant enough to stop taking the medication.”
“This side effect declines over time as people start to eat less and a new balance in eating is reached,” notes Sattar.
Most patients can still tolerate semaglutide and doctors now know to initially prescribe the drug at a low dose before slowly increasing it, he says. Patients are also given advice on how to limit this side effect, such as choosing easy-to-digest food, like soup and yoghurt, drink more water and avoid sugary and spicy foods, Sattar says.
It’s worth bearing in mind that semaglutide side effects, including digestive problems, seem to be worse among slimmer people who don’t have significant weight to lose, Cork notes. “While the risks associated with obesity far outweigh any risk associated with these drugs, that may not be the case for patients who are not obese but wish to take these drugs to lose a small amount of weight.
“The struggle now is to maintain the balance between what the drug was developed for, treating the disease of obesity, and what many in society want, to obtain the aesthetic ‘ideal’ of a slim body,” he says.
Losing weight quickly can also leave lips and cheeks looking less plump, sunken eyes and an overall hollowed look to the face, experts have warned. This effect is thought to be less severe if weight loss is gradual.
Sattar says people who are not obese but access semaglutide privately to lose weight may suffer this side effect, as he is not familiar with NHS patients complaining of this. “People can always reduce their dose or stop taking semaglutide for a while if they feel they prefer not to have sagging and wrinkled skin,” he adds.
Some semaglutide users have reported suffering from severe hair loss, being left with bald spots and receding hairlines. Photo / 123rf
Hair loss
As well as fat loss, some semaglutide users have reported suffering from severe hair loss, being left with bald spots and receding hairlines. The effect was reported among 3% of participants in a Wegovy clinical trial, compared to 1% of the placebo group, but is not listed as a side effect.
It is unclear what’s behind this effect but some experts have suggested it may be down to telogen effluvium – hair loss triggered by a change in the body, such as rapid weight loss. While this unpleasant side effect will stop when a person’s weight stabilises, the hair won’t necessarily grow back.
Reduces the risk of cancer
Being overweight or obese increases the risk of cancers – including breast, bowel and pancreatic – because excess body fat fires out signals to the body that tell cells to divide more often, which can lead to a tumour developing.
“As we believe weight is causally linked to several cancers, it makes sense that large scale weight loss will reduce cancer risks over time,” says Sattar.
A lower risk of cancer was not detected in the Select trial – the largest and longest study of semaglutide. Rates were the same regardless of whether patients were taking the drug.
However, subsequent research suggests the semaglutide can protect against the disease. One trial analysed data on more than 34,000 obese patients, who either used a weight-loss jab such as semaglutide, had undergone bariatric surgery or had no treatment over a 15-year period.
Results, presented at the American Society for Clinical Oncology conference in June, showed the risk of developing 13 weight-related cancers was 19% lower among weight-loss drug and bariatric surgery patients. Additionally, those taking the injection were less likely to die from the disease – suggesting the drugs directly prevent cancer.
Data from the Select trial found semaglutide lowers the risk of heart attacks, strokes and death due to cardiovascular disease. Photo / Getty Images
Boosts heart health
Scientists at UCL who looked at data from the Select trial found that semaglutide lowers the risk of heart attacks, strokes and death due to cardiovascular disease by a fifth.
Researchers believe this effect is not just a result of users achieving a healthier weight, but that semaglutide has an additional protective effect, says Sattar.
“This is likely a direct effect of the drug on the heart and blood vessels, [which are thought to] slow the development of the damaging plaques that lead to heart attacks,” he says.
Separate research showed a significant improvement in symptoms among semaglutide users living with heart failure with preserved ejection fraction – when the heart pumps normally but is too stiff to fill properly with blood. Obesity is a major contributor to the condition. “The results have really excited cardiologists,” says Sattar.
The researchers monitored 130,000 diabetes patients in the US for one year, who were taking Ozempic or other diabetes medication, and compared their rates of neurological conditions.
Results showed the risk of developing dementia was up to 48% lower among patients taking semaglutide, compared to other drugs. The team said this provides the “first robust evidence” the drug could boost brain health.
“We know the risk factors for dementia include higher blood pressure, strokes, heart attacks, high blood sugar level and obesity – and that GLP-1 receptor antagonists [the class of drug semaglutide belongs to] lower the risk of all of these,” says Sattar. “It makes sense they should lower the risk of dementia as well. There is also a suggestion that GLP-1 agonists may have a direct effect on the brain.”
A study from Imperial College London adds weight to this theory. Researchers tracked more than 200 patients with mild Alzheimer’s, half of whom were given liraglutide, which works in the same way as semaglutide. The drug appeared to reduce shrinking in parts of the brain that control memory, learning, language and decision making by almost 50%. Tests suggested cognitive decline was reduced by as much as 18%, after one year of treatment, suggesting the injections slowed the progression of disease.
Semaglutide is thought to reduce the desire to smoke. Photo / Getty Images
Helps quit smoking
Along with reducing the desire to eat, semaglutide is thought to reduce the desire to smoke – the leading cause of preventable death in Britain.
People taking the drug have anecdotally reported a reduced interest in smoking within a month of taking the drugs and this effect has been logged in animal studies.
Now, researchers, who monitored around 220,000 patients on diabetes medication, found that users were up to a third less likely to be diagnosed with tobacco addiction. The team, from the National Institute on Drug Abuse in the US, noted larger trials would be needed to confirm their finding.
