It’s been the hottest topic in weight-loss world. What’s not to love about the arrival of a “game-changing” drug that leads to losing 15 per cent of your body weight, in super-quick time, without having to slog through the misery of diet or exercise?
Wegovy – the brand name for this version of the drug semaglutide – was licensed to great fanfare in the UK earlier this year. It was expected to go on sale in pharmacies and weight-loss clinics any day now, but earlier this week, the launch was delayed, because suppliers fear the demand will be too high.
Semaglutide was originally a diabetes drug. It works by mimicking a hormone that regulates insulin levels and appetite. Two years after its blockbusting launch in the US, it was approved for use in the UK, and tens of thousands of people with obesity were due to start treatment imminently. Meanwhile, millions of people – including Jeremy Clarkson and Elon Musk – were getting their hands on private prescriptions.
They seem an exciting no-brainer, but are these drugs too good to be true? Alex Miras is a professor of endocrinology at Imperial College London. “What we don’t know for any of those drugs is what happens in the very long term,” Dr Miras says.
He explains that Wegovy has only been studied for two years. Saxenda, an older drug, has only been followed up for three. The new, exciting kid on the block, Tirzepatide, only has 18 months’ data. “On the other hand, these types of drugs have been used for diabetes treatment for 16 years, albeit at lower doses. I would be surprised, based on how they work and our experience so far, if we encountered an entirely new risk.”
So, what’s the truth about all the weight-loss drugs?
Wegovy
The one that was put on hold in the UK
What is it?
“Wegovy is a brand name of the drug semaglutide,” explains Dr Saira Hameed, a consultant in endocrinology and diabetes at Imperial College Healthcare NHS Trust and the author of The Full Diet.
What’s the difference between Ozempic and Wegovy?
They are the same drug, but Wegovy is available in higher doses.
How does it work?
Wegovy is designed to suppress your appetite, so you eat less. It mimics the action of a gut hormone called GLP-1, which is released after eating. It slows down the movement of food in your gut, so you stay full for longer. “These fullness hormones send a signal from the gut to the brain to indicate satiety,” says Dr Hameed. “The result is that people feel full even if they haven’t eaten, and when they do eat, they are satisfied with a smaller amount of food.”
Who is it for?
“Wegovy has now been approved for NHS use, but only under certain conditions,” says Hameed.
The new UK guidelines recommend Wegovy be prescribed to people who have a particular BMI (35 and over) and at least one weight-related health condition, such as diabetes or hypertension.
How effective is it?
In a clinical trial, published in the New England Journal of Medicine in 2021, Wegovy-treated participants lost about 15kg over a 68-week period. This equated to an average of about 15 per cent of their body weight.
But there is a caveat. When people stop taking Wegovy, they tend to put the weight back on. “A subset of people in the trial were followed up for a further year,” says Hameed. “Twelve months later, they had regained, on average, two-thirds of the weight they had lost on the drug.”
How is it taken?
Once a week, with a self-administered injection. The UK’s drug agency has approved its use for a maximum of two years, at a dose of up to 2.4mg.
Any side effects?
The most common side effect is nausea. Others include vomiting, abdominal pain, constipation, diarrhoea, acid reflux, wind, headache and fatigue. These tend to occur initially – for 95 per cent of people, they disappear within a couple of months.
More serious risks include gallstones and pancreatitis. The drugs should not be used during pregnancy, by women trying to get pregnant, or by breastfeeding mothers.
Ozempic
The one the celebrities have been getting
What is it?
Ozempic is the same drug as Wegovy, semaglutide, but administered at a lower dose.
How does it work and what are the side effects?
The same as Wegovy, above.
Who is it for?
“Ozempic is licensed in the UK, on the NHS, for the treatment of type 2 diabetes,” says Dr Hameed. “It’s usually only prescribed when tablets have not sufficiently controlled blood glucose levels.”
However, it can also be prescribed privately for weight loss, which is how celebrities and high-flyers have been able to obtain it.
How effective is it?
“Because Ozempic hasn’t been trialled for weight loss, it hasn’t been licensed for this use,” says Hameed. A study of people with type 2 diabetes concluded that people taking the maximum dose of 1mg a week lost an average of a stone (6.3kg).
How is it taken?
Also as a self-administered injection, at a dose of up to 1mg once a week.
Saxenda
The drug that’s been around for a while
What is it?
Saxenda (generic name liraglutide) is an antidiabetic medication used to treat type 2 diabetes and chronic obesity.
How does it work?
“Like Wegovy and Ozempic, Saxenda also mimics the hormone GLP-1, leading to a feeling of fullness,” explains Dr Hameed. But it has a shorter “half-life” than Ozempic and Wegovy, and has to be taken every day.
Who is it for?
Saxenda is prescribed via specialist NHS weight-loss services for people with a BMI of 35 or above, who have prediabetes and at least one cardiovascular risk factor, such as hypertension or high cholesterol.
In the UK, you must lose at least 5 per cent of your body weight after 12 weeks on the full dose in order to continue with the medication.
How effective is it?
Trial data suggest that people taking Saxenda for 56 weeks lose, on average, 8.4kg, or 8 per cent of their body weight.
As with Ozempic and Wegovy, people put the weight back on when they stop: in this case, an average of 2.9kg after 12 weeks.
How is it taken?
Also as a self-administered injection, at a dose of up to 3mg every day.
Any side effects?
As Saxenda is from the same class of drugs as Ozempic and Wegovy, the side effects and contraindications are the same.
Tirzepatide
The new cutting-edge kid on the block
What is it?
“This is a really impressive medication,” says Dr Miras. “What makes it unique is that it combines synthetic analogues of two hormones – GLP-1 and GIP – which stimulates insulin secretion.” Both, he explains, are naturally occurring hormones that we all produce in our intestines when we eat.
How does it work and who is it for?
The combination of these two hormones helps to suppress appetite and also to control blood sugar. “In the US, Tirzepatide has already been approved for adults with diabetes, because it causes very profound reductions in glucose,” Miras says. While it is not yet available to anyone in the UK, Tirzepatide is currently being assessed for the treatment of obesity, too.
How effective is it?
“Randomised control clinical trials have shown that it causes about 22 per cent weight loss,” Miras says. “We’re getting into weight-loss territories that only bariatric surgery is able to achieve. That’s why we’re so excited.”
How is it taken?
An injection, once a week.
Any side effects?
Clinical trials have compared its effect on people with diabetes to those of Ozempic. “What they’ve found is the side effects are very similar: nausea, constipation, diarrhoea,” Miras says.
Imcivree
The drug for rare genetic disorders that cause obesity
What is it?
Sold as Imcivree, setmelanotide is a drug that reduces appetite through direct action on the brain’s appetite-control centre – the hypothalamus. But only for a small minority of people.
How does it work and who is it for?
“In very rare cases, obesity is caused by genetic disorders, which impair appetite control by the hypothalamus,” explains Dr Hameed. “Patients with genetic obesity syndromes experience extreme hunger and almost always develop severe obesity in very early childhood. They might weigh up to 25kg by the age of two.”
Setmelanotide is only used under expert supervision and in patients whose obesity, after genetic testing, has been shown to have a specific cause.
How effective is it?
In trials, people lose an average of 10 per cent of their body weight. “But it is very important to stress that these trials were done in people with defective appetite regulation caused by a genetic disorder,” says Hameed.
Plus: “Weight loss and control of hunger will only continue for as long as setmelanotide is taken.”
How is it taken?
As a daily injection.
Any side effects?
Side effects include skin reactions at the injection site, darkened patches of skin, headache, nausea and diarrhoea. Depression and suicidal thoughts have also been reported.
Orlistat
The older option
What is it and how does it work?
A drug that has been in use since the 1990s, “Orlistat works by reducing the amount of fat that people absorb from their gut when they eat,” says Dr Miras.
Who is it for?
The NHS will prescribe orlistat to people with a BMI of 30 or more, or those with a BMI of more than 28 who also have a risk factor such as type 2 diabetes, hypertension or familial high cholesterol.
How is it taken?
In tablet form, before meals. “It makes people excrete 30 per cent of fat from their foods,” says Miras. “The resulting diarrhoea is so unpleasant, it effectively punishes you for having eaten fat. It makes the person learn to cut down on the fat in their diet. When that happens, and there are people who do that, then these people do well with their weight loss.”
How effective is it and any side effects?
“The weight loss is small, and the side effect – diarrhoea – is pretty severe,” Miras says.
The over-the-counter options
If you would rather pop down to the chemist, which over-the-counter options are the most promising?
Green coffee bean extract, in pill or powder form, is currently popular and, says Dr Hameed, it “probably has a small effect on weight loss by increasing metabolism, similar to drinking caffeinated drinks. A few short-term randomised clinical trials show it might help with losing a few pounds, but more robust, longer-term studies are definitely needed before any definitive conclusions can be drawn.”
Raspberry ketones: “Some in-vitro cellular experiments [in test tubes], as well as rodent studies, suggest that they may support weight loss by reducing food consumption, as well as increasing body-fat breakdown,” Hameed says. “However, there is no good evidence from human studies to show that these supplements help with weight loss.”
Green tea extract has been linked to liver damage and even liver failure. When it comes to supposed weight-loss properties, “The data are quite promising for mice. So if your pet rodent has a weight problem, you might be onto something. But for humans? The data are pretty limited,” says Dr Duane Mellor, senior teaching fellow at Aston Medical School and a spokesman for the British Dietetic Association.
