How exactly do weight-loss drugs work – and which ones are best?

Telegraph

a day ago

When it comes to weight loss, we're all after a magic bullet, a simple, stress-free way of shedding the excess pounds. And so for millions around the world, the arrival of the so-called GLP-1 class of weight-loss drugs in 2021 seemed like a godsend, especially for anyone who's struggled to stick with dieting advice, commit to an exercise regime or simply find a weight-loss solution that works.
Named after the GLP-1 hormone they mimic in the brain, the drugs help you stay full longer and reduce appetite.
But while drugs such as Wegovy and Mounjaro are now household names, they aren't as easy to access on the NHS as many would hope. People willing to pay can now get them via a range of private clinics and online doctor services, although legitimate services will not prescribe them to you unless you have a BMI of 27 or higher, in accordance with guidelines. However, with patents starting to expire and the cost of these medications predicted to fall, as well as future GLP-1 drugs which are promised to be even more effective now in the pipeline, the future of weight-loss treatments seems promising.
So with that in mind, how exactly do GLP-1 drugs work, what's out there, and who is eligible to get them?
What are GLP-1s?
The different types
Which is best for weight loss?
Side effects
Cost
What are GLP-1s and how did it all start?
The story of a drug market, and the origins of GLP-1, now worth hundreds of billions, began with a surprise discovery at Massachusetts General Hospital in the 1980s.
Svetlana Mojsov, a biochemist at The Rockefeller University, carried out a series of experiments which revealed that the gut releases a hormone called GLP-1 in response to eating, stimulating the release of insulin in the pancreas. Further research would later show that GLP-1 also acts on the brain to signal that we're satiated and dampen down appetite.
Over more than two decades, scientists at Danish pharmaceutical company Novo Nordisk and American pharma Eli Lilly would work to develop synthetic versions of this natural hormone; injectable medications called GLP-1 receptor agonists, or more commonly, GLP-1s. The idea was that they would bind to and activate the same biological pathways in the body as the real thing, but in a vastly more potent fashion which lasted for days at a time.
GLP-1s were initially marketed to Type 2 diabetes patients because of their ability to stimulate the production of insulin when blood sugar levels are excessively high. The more recent suite of medications are administered in higher doses, with the primary goal of facilitating weight loss.
'The drugs that work on this system are much more powerful than the natural GLP-1 hormone,' explains Prof John Wilding, an expert in obesity, diabetes and endocrinology at the University of Liverpool. 'The natural hormone is broken down within a few minutes, whereas you inject the drugs and they last in the body for a week or longer.'
How do the GLP-1 drugs work?
Scientists have discovered that both the vagus nerve – a vast chain of nerve fibres which spans the body – and the brain itself, is studded with so-called GLP-1 receptors. These are proteins which can be specifically stimulated by either the body's own GLP-1 hormones produced by the gut, or synthetic GLP-1 drugs such as Ozempic and Mounjaro.
Wilding says that the presence of GLP-1 receptors in the brain is thought to be one of the key reasons why GLP-1 drugs can impact hunger, fullness and reward, as they allow these drugs to stimulate various brain regions, swiftly dampening down appetite and the desire to overeat.
But beyond weight loss, there also may be some unforeseen, even more profound, consequences of stimulating GLP-1 receptors in the brain which is why GLP-1 drugs are also being studied for conditions ranging from addiction to neurodegenerative diseases. Because these receptors are not only found in the brain, but across the body, including in organs such as the kidney and the heart, they may also have beneficial consequences when it comes to preventing and even treating a range of chronic diseases.
The different types of GLP-1 drugs
1. Liraglutide (Saxenda)
Good for low levels of weight loss
It didn't make as many headlines as Ozempic, yet a different drug known as Saxenda was actually the first GLP-1 to become available on the NHS for treating obesity, back in October 2020.
A daily rather than weekly injection, it isn't quite as powerful or as long-lasting as the newer alternatives which has led to Saxenda being eclipsed. 'There's been two or three generations of these drugs,' says Prof Wilding. 'The initial ones have mostly disappeared from the market because they were once or even twice a day injections, and relatively weak compared to what we've got now. But Saxenda is still available and has some effect on body weight.'
More notably, Saxenda's UK patent expired last month and the so-called generics industry – which produces non-branded copies of existing drugs – has already developed copies of liraglutide which are expected to be considerably cheaper than other GLP-1s, potentially boosting its appeal.
2. Semaglutide (Ozempic/Wegovy)
Good for building up the dosage more slowly
A weekly GLP-1 injection, semaglutide is marketed as Ozempic for the treatment of Type 2 diabetes and Wegovy for the treatment of obesity.
Wilding explains that the main difference between Ozempic and Wegovy is that the latter offers a slightly higher maximum dose of semaglutide which people can work their way up to using. 'For diabetes the dose usually only goes up to one milligram,' he says. 'But with Wegovy, the maximum dose is 2.4mg.'
Compared with Saxenda, it's not only longer-acting but the reach of the drug also seems to be more potent. 'We know from some of the preclinical studies in mice that semaglutide seems to reach parts of the brain that liraglutide doesn't reach,' says Wilding.
3. Tirzepatide (Mounjaro)
Good for higher amounts of weight loss
The most powerful weight loss drug on offer, Mounjaro is slightly more complex than either Saxenda or Wegovy. As well as activating the body's GLP-1 receptors, it also stimulates receptors used by a second gut hormone called GIP.
'What the gut hormone is doing is helping the GLP-1 work better,' says Martin Whyte, an associate professor of metabolic medicine at the University of Surrey. 'So it's almost like a super GLP-1.'
Prof Wilding points out that Mounjaro also comes in six different doses, with the 5mg dose offering similar weight loss benefits to Wegovy, and then the higher 10mg and 15mg doses helping patients to lose even more weight.
4. Retatrutide
The most powerful weight loss drug
This isn't yet clinically available but retatrutide already created something of a stir in the obesity medicine world on the back of clinical trials which suggest that it's the most powerful weight loss drug created so far.
Developed by Eli Lilly, makers of Mounjaro, you'll hear retatrutide described as a 'triple agonist,' which means that it mimics the effects of three gut hormones: GLP-1, GIP and another one called glucagon. This means that it doesn't just blunt appetite, it also speeds up the metabolism of body fat.
Currently being studied in a phase three trial, it could feasibly hit the market in the next couple of years. There's more expected to come as well with more than 100 different drugs based on various gut hormones in different stages of clinical development.
'We're going to see a lot of competition and interest in this area, because now people know it can be done,' says Prof Wilding. 'That's probably a good thing, because it means more choice for patients. Maybe somebody who doesn't tolerate one will be able to take another one, so having a range of options available is good.'
Which GLP-1 drug is the best for weight-loss?
The following table shows the average percentage weight-loss for each GLP-1 drug:
Dr Whyte says that when he treats patients with obesity, he now almost always prescribes Mounjaro because the weight loss effects are clearly superior to anything else currently available.
'In terms of weight loss, there's a very good argument to just use tirzepatide and not semaglutide full stop,' he says.
This could change again if retatrutide is approved for mainstream use in the coming years. However, Dr Whyte predicts that the emergence of more options will allow doctors to make more tailored choices.
'In many individuals, you don't need 20 per cent weight loss,' he says. 'The data shows that if your BMI is less than 35, something like 7 per cent weight loss can already achieve a clear metabolic benefit. So something like semaglutide would be perfectly reasonable and would do the job just as well.'
What are the other health benefits?
GLP-1 drugs have also been linked to other health benefits besides weight loss. They have been shown to help reduce the risk of:
Sleep apnoea
Addiction
Cardiovascular disease
Chronic kidney disease
Obesity-related cancers
Non-alcoholic fatty liver disease
Dementia
From curbing alcohol addictions to reducing the risk of Alzheimer's disease, GLP-1s have the potential to become game-changing medications for an entire plethora of other conditions.
Some benefits are, of course, a direct result of weight loss. Tirzepatide is now approved by regulators in the United States as a treatment for obstructive sleep apnoea, a dangerous midlife condition exacerbated by excess weight where breathing stops and starts dozens or hundreds of times during sleep, while research presented at the 2025 European Congress on Obesity showed that GLP-1s can almost halve the risk of obesity-related cancers.
Semaglutide is also officially recognised by regulators as reducing risk of heart attack and stroke in people at higher risk of these conditions. 'We see improvements in things like cholesterol and other fats in the blood [when people take GLP-1s],' says Prof Wilding. 'Bad fats tend to go down and good fats tend to go up. We see lowering of blood pressure and general improvements in quality of life.'
But research is also showing that GLP-1s can have even broader effects, curbing cravings for alcohol and other substances in people with long-term addictions, something which scientists believe relates to the impact of these drugs on reward pathways in the brain.
Most fascinatingly of all, clinical trials are now formally testing whether these drugs can protect against the onset and progression of dementia in people with mild cognitive impairment, with studies in animals suggesting it can reduce inflammation in the brain and stimulate the repair of damaged nerve cells.
What are the side effects?
As with most drugs, there are downsides. These include:
Nausea
Constipation or diarrhoea
Gallstones
Pancreatitis
Hypoglycaemia
Allergic reactions
Prof Wilding says that the majority of people who take GLP-1 drugs can expect some side effects, most commonly nausea and gastrointestinal (GI) problems such as constipation or diarrhoea. In a small number of cases, these issues can prove so intolerable that users end up quitting the medication, but the majority of users are able to cope by slowly tapering up the dose over time.
'If you look at the trials, 80-90 per cent of the people are able to stay on the medicine, but there are a significant minority who can't, just because of these GI side effects,' says Prof Wilding.
Much rarer problems can also occur such as the formation of gallstones, which Wilding says can be a side effect of any form of weight loss, as well as pancreatitis or inflammation of the pancreas. 'This can be a very serious medical condition which can be related to gallstones,' he adds.
Because of the risk of side effects, researchers are keen to emphasise that these drugs are not benign and should be used with caution. In April 2025, researchers from the US Centres for Disease Control and Prevention assessed data from thousands of emergency department visits which had been directly linked to semaglutide. While gastrointestinal side effects were the main reason, the data showed that some patients also experienced allergic reactions to the drug and a sudden drop in blood sugars levels, known as hypoglycaemia, which in some cases required hospitalisation.
'It may be that semaglutide interacts with other medications, or that some people who use semaglutide stop eating to the point of severe hypoglycaemia,' says Dr Pieter Cohen, an associate professor at Harvard Medical School and one of the study authors.
According to Dr Whyte, side effects are less common with tirzepatide and there is a hope that this will also be the case with retatrutide.
How available are GLP-1 weight-loss drugs?
Despite the clamour for GLP-1s, their availability in the UK is still relatively restricted on the NHS. Drugs such as Wegovy and Mounjaro are only available to people with a body mass index (BMI) of at least 35, as well as at least one obesity-related health problem such as high blood pressure, high cholesterol, Type 2 diabetes or sleep apnoea.
On a private basis though, the restrictions are less strict. The drugs are officially licenced to be given to people with a BMI of over 30 or, as Dr Whyte says, doctors will prescribe it to people with a BMI over 27 providing that their weight is impacting their health. 'I'm not afraid to use it if they've got a BMI of 28 and significant fatty liver disease, or polycystic ovarian syndrome and they're struggling to conceive, that sort of thing,' says Whyte.
Dr Whyte predicts that the prescribing of GLP-1s will become more nuanced than just the relatively arbitrary BMI figure. Instead, he says that tools such as bioimpedance scanners - smart scales which run a small, imperceptible electric current through your body to estimate your percentage of body fat – waist circumference and waist-to-hip ratio, will be used to determine who can benefit most.
'Hopefully licences for things like GLP-1s won't just be based on a BMI number,' he says. 'It will be about getting more of a grip on how much fat there is, whether it's abdominally distributed, which is more harmful, and then looking at the health consequences for that individual.'
How much do they cost?
The exact prices vary per clinic, as many services offer package deals which also incorporate weight loss coaching and advice alongside the drugs themselves. However, here are some prices offered by Asda and Superdrug Online Doctor services.
Liraglutide (Saxenda)
Saxenda is currently out of stock in the UK, both on the NHS and across private services. However according to Asda Online Doctor, a generic version of Saxenda is now available under the name of Nevolat, with prices starting from £127.00
Semaglutide (Wegovy)
According to Superdrug Online Doctor, monthly prices for Wegovy begin from £195 per month for the lowest dose regimen (0.25mg/week). The highest dosing plan (2.4mg/week) costs £295 per month.
Tirzepatide (Mounjaro)
Again prices vary from £215 per month for the lowest dose (2.5mg/week) to £245 per month for the highest dose (15mg/week), according to Superdrug Online Doctor.