When Elon Musk revealed the secrets behind his dramatic 13.6kg weight-loss on X in November 2022, it was the first time many people had heard the words ‘Ozempic’ and ‘Wegovy’ – the “miraculous” weight-loss drugs feted by doctors and celebrities. Headlines were made. Internet searches spiked.
But how many of us recall that Musk also said he’d been fasting? And stopped keeping snacks within reach? Or that the drug gave him “next-level” sulphur burps that taste like rotten eggs?
It is human nature to focus on the things we want to hear, like news of amazing new weight-loss drugs, not the dull bits, like dietary change, sensible lifestyle habits or grim side-effects. And that’s a problem. These drugs are truly exciting, but there are huge gaps in the public discourse. It is time to look deeper.
We know from studies that Wegovy – manufactured by Novo Nordisk, the Danish pharmaceutical giant – can cause life-changing weight-loss of 15.2%, which equates to 15.9kg for most subjects: like hacking 16 bags of sugar from your body.
Respected obesity experts have called the drug a “game changer.” But prescriptions are currently limited to two years, with research predictably confirming that people regain two-thirds of their weight when they stop, and Novo Nordisk warning of full weight regain within five years. Potent weapon, yes. Miracle cure, no.
A faster route to fat loss
The drug works quickly, with a 15% weight-loss achievable within 16 months. But in every single trial the subjects also engaged in healthy lifestyle change, received health counselling, and used familiar old strategies like low-calorie diets, exercise and food diaries.
Will these bits get forgotten? And while most people lose weight, research shows that, for unknown reasons – possibly metabolic, hormonal or psychosocial – for 1 in 10 people the drug is ineffective, leaving a bitterly disappointed minority.
Most subjects successfully finished the semaglutide trials, but 89.7% suffered from side effects including diarrhoea and vomitingThe New England Journal of Medicine
Most subjects successfully finished the trials, but 89.7% suffered from side effects, like diarrhoea and vomiting. And Novo Nordisk has admitted the drug is linked to cancerous thyroid tumours in rodent studies. That’s not an insignificant concern. Deeper research continues apace.
Studies suggest the revolutionary drug could cut heart attacks by 20%. But the European Medicines Agency is now investigating possible links to “suicidal ideation and self-injurious ideation” (suicidal thoughts and self-harm). You won’t see that on TikTok’s 248k #MyWegovyjourney posts.
Make no mistake: this is an exciting new treatment. But huge ethical, social and medical questions remain. How widely will the drugs be used, and for how long? What are the side-effects? And who should get the drugs? The U.S. Food and Drug Administration (FDA) has approved the drug for 12-18 year-olds with obesity, with Novo Nordisk now doing trials with children as young as 6.
Are we witnessing the arrival of a miraculous, life-changing preventive medicine which will end the obesity crisis? Or the grim spectre of a lifelong dependence on drugs first injected into kids when they still believe in Santa? Will people neglect healthy lifestyle change and become hooked on big pharma? Or are these wonder-drugs our best hope yet?
The search for a global solution
Given the scale of the obesity crisis, the buzz around these drugs is understandable. The World Health Organisation (WHO) says 2.5 billion adults are overweight (with a BMI of 25 or over) or obese (BMI of 30 or over), with 51% of the world’s population forecast to be overweight or obese by 2035, putting billions at elevated risk of heart disease, diabetes, cancer, musculoskeletal disorders and premature death.
The potential of these drugs is therefore stratospheric. In September 2023, Novo Nordisk became Europe’s most valuable firm, with its stock market valuation of $428bn eclipsing LVMH – owner of 75 luxury brands like Louis Vuitton, Moet Hublot and Dior. It is now worth more than the entire Danish economy (£323bn).
According to investment bank Jefferies, this new class of drugs could become a $150bn market by 2031, comparable in size to the cancer drug market. And next-generation drugs are already being cooked up by rivals. Eli Lilly’s Retatrutide can achieve a weight loss of 24.2% – a quarter of a person’s entire body mass. Wow.
The sweet-spot solution
Weight-loss drugs have long been seen as the Holy Grail for obesity, being more widely available and less invasive than bariatric surgery, and easier and more successful than dietary or exercise interventions. But until now they have been only mildly successful. Liraglutide, marketed as Saxenda, offered a weight-loss of 6% and required daily injections. And Orlistat, marketed as Xenical, required 3 daily tablets and led to a 5% weight loss.
But semaglutide – the magic ingredient in Wegovy – is three times more potent. It’s an example of a class of drugs called Glucagon-like peptide-1 (GLP-1) receptor agonists. These mimic the GLP-1 hormone released in the gut after eating, making us feel fuller so we eat less. The drug, taken weekly using injection pens, also slows digestion and boosts the release of insulin after eating, which helps to control blood sugar levels.
Patients are now very well informed. And they will be asking for it.Dr Stephen Lawrence, University of Warwick
Semaglutide was originally used to treat diabetes, under the Novo Nordisk brand Ozempic, but its weight-loss effects meant it was soon used “off-label” by celebrities. Scientists pivoted to exploring its weight-loss potential, leading to the creation of Wegovy, which has a higher dose of semaglutide and is now approved specifically for weight loss. In the UK the drug is available through the NHS only to patients with obesity via specialist services, but the drug will be available through doctors, pharmacists like Boots, and private or online clinics. Some already have it.
Dr Stephen Lawrence, a GP, diabetes specialist and Associate Clinical Professor at the University of Warwick, says the drug is a “fantastic” biotechnological achievement. “I remember thinking back in the noughties that if this works for people with diabetes, potentially it might be an option for people with obesity.” Amazingly, the drug represents a laboratory copy of a chemical agent found in the saliva of a specific lizard called the Gila monster living in the US and parts of Mexico.
This exciting innovation is now “coming of age,” he says. “There’s been nothing really that has been anywhere near as successful as the GLP-1 receptor agonists. And for that reason, I think every legitimate prescriber will be reaching for this. Not least because patients are now very well informed. And they will be asking for it.”
Solid scientific support
Wegovy comes with serious scientific backing. A 2021 study found that, as well as that headline-making 15% drop in bodyweight, subjects reduced their cardiovascular risk factors and improved their physical function, freeing them to engage in more exercise. A 2020 study revealed that subjects ate 35% less food – around 940kcal less per day – and reported increased fullness and reduced cravings. And a 2022 study reported that the drug triggered a huge 14.4cm drop in waist circumference over two years, plus improvements in health markers such as blood pressure and cholesterol.
Research suggests 9 out of 10 people will lose 5% of their bodyweight, 7 out of 10 will lose 10%, and 5 out of 10 will achieve that headline figure of 15% or more. But 1 in 10 won’t lose weight. Where each person will fall along that curve is unpredictable.
Weight management is hard… it affects people’s quality of life, their ability to get jobs evenDr Duane Mellor, Aston Medical School
Still, for the majority this is life-changing stuff. “Anyone who doesn’t have a weight problem may find it difficult to put themselves in the position of that person who is overweight or obese,” explains Dr Lawrence. “When you lose anything more than 5% of your body weight, you are starting to see clinically meaningful results. Certainty at 10%. So it is difficult to argue against making this drug available to people who need it.” He adds that this will not just help someone avoid heart disease and diabetes, but weight is also linked to everything from mental health to dating success.
Dietitian Dr Duane Mellor of Aston Medical School also welcomes the new jabs. “It is really good to have a new product and new solution or tool in the box, because weight management is hard,” he says. “And it affects people’s quality of life, their ability to get jobs even, all the way through to short- and long-term health outcomes.”
The costliest cure
Right now, the main problem is logistics, with stocks running low – a huge concern for people with diabetes. “The success of the drug is almost its downfall,” says Dr Lawrence. “There are 4.9 million people in the UK with diabetes, so you’re talking about one in 15 people in the nation. Whereas 66% of adults are either overweight or obese. So once these people access the drug, there is no pharmaceutical company in the world that’s going to be able to keep up with demand.”
If every American with obesity were on Wegovy, the total cost would be 10% of the entire U.S. economy – that’s $2.1 trillionThe Atlantic
The costs will be astronomical too. The NHS list price for a month’s supply is £73.25 to £175.80, though contractual agreements will make this lower. But in America the drug is costing people $10-15k per year. As highlighted by The Atlantic magazine, if every American with obesity were on the drug, the total cost would be 10% of the entire U.S. economy, or $2.1 trillion. Two thirds of the population is overweight or obese. The drugs cost $10-15k per year. And they may be needed for life. Big Pharma is getting rich.
The price of the drugs will fall as competitors arrive and production improves. And the savings caused by reductions in obesity-related health issues are potentially colossal. But these are still eye-watering figures. And in the short-term, we may see an exacerbation of existing inequalities, with the drug funnelled to private clinics and rich people. “Is it going to be used equitably to those with the greatest need, or those who just had the financial and vocal power to go and ask for it?” asks Dr Mellor.
He also worries whether private clinics will offer the parallel lifestyle, dietary and psychological support for long-term weight-loss, and if the NHS will have enough staff to do the same for millions of people. He uses the analogy of a piece of flat pack furniture: “Do we have all the instructions and all the pieces in the box to actually build the wardrobe, rather than just finding out we have a fancy new screwdriver?”
Solutions and side-effects
With #Wegovy already amassing 553 million views on TikTok, demand will undoubtedly be huge. And when the drug’s use expands across society, side-effects will quickly be exposed. This has been the downfall for other promising weight-loss drugs. Rimonabant, produced by Sanofi, was approved in Europe in 2006, under the brand name Acomplia, but withdrawn in 2008 when it was found to double the risk of psychiatric disorders. And Lorcaserin, marketed as Belviq by Arena Pharmaceuticals, was approved in 2012 but banned in 2020 when it was linked to cancer. The hype around Wegovy suggests people aren’t going to wait to find out.
Each time a new drug is launched there’s a big hurrah… six months later it’s taken off the market, very quietly, because it has side effectsProfessor Jane Ogden, University of Surrey
This is a concern for Jane Ogden, Professor of Health Psychology at the University of Surrey. “Each time a new drug is launched on the market, there’s a big hurrah, everyone’s very excited, people seem to lose weight and then usually about six months later, it gets taken off the market, very quietly, because it has side effects.” Though optimistic, she retains “a little bit of scepticism.”
Wegovy warns of common side-effects such as nausea, diarrhoea, vomiting, constipation, stomach pain, headaches, fatigue, dizziness, bloating, belching, gas, stomach flu, heartburn and a runny nose or sore throat. On social media, there are reports of people spending the weekend locked in their bathroom. Studies suggest most symptoms will be “mild-to-moderate,” but 6.78% will discontinue treatment as a result. “By far the majority of people will have mild symptoms such as diarrhoea, constipation, nausea or abdominal pain, which settles down within a few weeks,” says Dr Lawrence. “But there’ll be a proportion of people for whom those symptoms become so prolonged they should not be continuing.”
A 2020 study found that 70% of people who took GLP-1 drugs for diabetes stopped taking them within two years, perhaps through side effects or boredom. “Adherence rates are not always great for medication,” says Professor Ogden. Even Professor Jens Juul Holst, one of the scientists who pioneered the drug, has warned that some people may lose all pleasure in food, making life so “miserably boring” that they quit.
Wegovy also flags up “serious” potential side effects, such as “possible thyroid tumours, including cancer,” based on rodent studies, as well as inflammation of the pancreas (pancreatitis), gallbladder and kidney problems and elevated heart rates. Anecdotally, people also notice some facial ageing – dubbed “Ozempic face”.
The longer-term side effects remain a mystery. “If there’s a fear around these drugs, it is that with the very rapid adoption of these drugs, which has been fuelled and catalysed by celebrity endorsement, it’s actually overtaken the natural development and progression of the drug,” says Dr Lawrence. “Normally it would take a number of years to get to this degree of success and popularity. But this, coupled with social media and celebrity endorsement, means you have a drug which is highly desirable getting to large masses of the population – and there are potential side effects.”
A cure at all costs?
Fortunately, as semaglutide has been used for diabetes for a while, we are already relatively far down the line. But people’s need – or desperation – to lose weight could be an issue. “You may find that some people think, well, I’m not going to report these symptoms, because I don’t want to be taken off the medication,” warns Dr Lawrence.
Some doctors have expressed concerns about the under-reported loss of muscle mass and bone density which accompanies this huge weight-loss. This could affect the body’s fat-burning metabolism and enhance risk of injuries, osteoporosis, heart disease and diabetes. One study found that 40% of the weight loss triggered by semaglutide is from lean mass, such as muscle and bone, with subjects losing 10.4% fat mass, and 6.9% lean mass. As a result, doctors are warning users to eat more protein and do muscle-building resistance training.
But how many people know this? And how many will do the gym work? Some may just enjoy watching the number on the scales plummet, regardless of whether they are losing fat, muscle or bone.
The “medicalisation of obesity”
This critical issue raises the wider question of whether people will respect the parallel healthy lifestyle changes required alongside the drug intervention. Will people eat more healthily and do more exercise, or sit on the sofa, eat rubbish and expect the drug to work its magic? Without aerobic exercise, you won’t strengthen your heart and lungs. Without resistance training, you won’t maintain muscle mass. And without healthier food choices, you won’t get enough key vitamins and minerals.
“My biggest concern as a psychologist is this this is all part of the medicalisation of obesity: the desperate search for a medical solution, something which will magically take the control out of the individual and not require individual behaviour change,” says Professor Ogden.
Dr Mellor agrees that the drug “may help you against the volume of food that you wish to consume, but it doesn’t necessarily help navigate the choice.” That’s why serious lifestyle change is critical. “You need to change the choice of food, as well as looking at portion control and the amount of eating episodes.”
“You need to use [drugs] in a way that allows you to reevaluate your relationship with food and physical activity, rather than “I’ve got a drug now – I can eat what I like”Dr Duane Mellor, Aston Medical School
Though supportive of the drug, Dr Lawrence has concerns about its “magic bullet” appeal. “That’s not because people aren’t intelligent, because I think the general public is very well-informed,” he says. “But the problem comes when something is celebrity-endorsed. I’m not criticising celebrities. I’m saying that this means it goes through the population very quickly – and people will focus on what they want.”
Just like with that headline-making Elon Musk tweet, we – and the media – zero in on the bits we want to hear, not the bits we need to hear. These drugs are a brilliant tool, but their success depends on education, support and an authentic commitment to lifestyle change. Dr Lawrence says the drugs may carrying warnings, like on cigarette packets, which stress that weight-loss is only achieved along with dietary and lifestyle change.
Dr Mellor worries that some people may see any NHS-prescribed sessions with a psychologist or dietitian as “the hoops you’ve got to go through to get the drug. Then it gets forgotten.” The drug can be “potent and effective,” he says, but the problem is the way it may be marketed or managed. “You need to use it in a way that allows you to reevaluate your relationship with food and physical activity,” he says. “Rather than: oh, I’ve got a drug now, things are fine, I can eat what I like.”
Medicating for life
As studies clearly demonstrate, without parallel health support and a commitment to healthy change, a person’s weight will simply soar when they come off the drug. “You’ve got to learn from the way you live when you’re on the drug and transfer that into the future when you’re not on the drug – and that’s what’s difficult,” says Professor Ogden. “I think that’s why we get weight regain when people come off the drug now, because they haven’t actually changed their behaviour.”
This begs a key question: might people have to stay on the drug for life? The current two-year limit may change, and Dr Lawrence points out that people with high blood pressure or diabetes take medication longer-term. “We don’t say: ‘Great, you’ve maintained levels now for a year or two years, so we’re going to take the treatment away,’” he says. “And therefore it seems a bit churlish to apply the same rule to people with regards to weight loss. Because if someone struggles with weight, they are going to, in all likelihood, do so for a long period of time, in fact the rest of their lives.” The drug treatment may be “continuous or intermittent,” he says.
Health bodies will have to do some meaty calculations to work out whether the cost of supplying a lifetime of medication for millions may outweigh the spiralling costs of the raging obesity epidemic. But Dr Mellor says we cannot just buy our way out of a health crisis, or downplay key issues like healthy eating, affordable food, cooking skills, taxes, family health advice, environmental change and exercise. “We cannot medicate everybody,” he says. “We wouldn’t want to medicate everyone because it is not ethical.”
Ignoring the origins of obesity
Many academics worry that the success of these drugs will be mirrored in research budgets and government focus, with investment in pharmaceutical companies soaring, while funds for research into the environmental, dietary, metabolic and social causes of obesity drying up, and government plans for food taxes, labelling and health education disappearing. That would be a toxic result for the next generation.
In a journal article, Dr David Ludwig, an obesity specialist at Boston Children’s Hospital, and Professor Jens Juul Holst teamed up to warn that “treatment focused on the root cause of disease generally achieves the best outcomes.” We should be researching dietary and behaviour change, not just drugs or surgery.
Treatment focused on the root cause of disease generally achieves the best outcomesDr David Ludwig and Professor Jens Juul Holst
One in five children in America have obesity, with about the same prevalence in the UK. Does this mean that one in five kids may be given the drugs? Potentially for life? Research has shown that 44.9% of teens using semaglutide are no longer clinically obese after 16 months.
That’s miraculous and would seriously limit the complications of obesity, from damaged organs to diabetes, at a young age. But the drugs may disincentivise kids to adopt healthy habits and lead to an early-age dependence on pharmaceutical solutions. These huge ethical issues need serious consideration.
But as Giles Yeo, Professor of Molecular Neuroendocrinology at the University of Cambridge, has pointed out, the two strategies are not mutually exclusive. “These drugs are designed to treat obesity. Prevention will require tackling poverty and improving our diets, and that does indeed need policy change. We may well get to the point where obesity is no longer a problem; till then, the drugs are a useful tool.”
Kick-start healthier living
The sincere hope among doctors is that these weight-loss drugs will not be needed for life and will not hamper vital research into the underlying causes of obesity. They will simply be used to kickstart a person’s weight-loss journey, leading to healthier habits and increased exercise levels, thanks to improved mobility and confidence. Dr Ogden says it’s hard to tell a patient to lose two pounds a week for 15 years, given the “slow degree of reward.” But these powerful, fast-acting drugs can be a potent psychological springboard.
“That’s going to make someone feel better about themselves, they’re going to be able to fit into clothes that they couldn’t fit into before, they’re going to be able to be more active, that self-esteem is going to then spiral up, so they are going to eat more healthfully, they’re going to feel happier about themselves and they are going to do more exercise that will then cause more weight loss.”
Make someone feel better about themselves… self-esteem is going to spiral up, so they are going to eat more healthfully [and] do more exerciseProfessor Jane Ogden, University of Surrey
However, all the evidence so far suggests people just pile on the weight when they come off the drugs. And if people really will need the drugs for life, are we sleepwalking into a pharma-fed future? And what might that existence feel like? For example, it appears that the drugs influence the brain’s reward centres, with users reporting not just a reduced addiction to cakes but also to shopping, alcohol, gambling – even nail-biting.
In fact, Kyle Simmons, a professor of pharmacology and physiology at Oklahoma State University, is now researching the drug’s addiction-curing potential. But like Professor Jens Juul Holst, he has warned that anhedonia (the reduced ability to experience pleasure) could cause a loss of interest in pleasure more generally, which “might not be a great thing.” What if the drugs reduce your quality of life as well as your belt size? Would you agree to that deal?
Big pharma betting the bank
The research continues. But Big Pharma is already cooking up an exciting second generation of weight-loss drugs. Mounjaro, the brand name of the drug tirzepatide, produced by Eli Lilly, has been shown to achieve up to 22.5% weight-loss. And Retatrutide, another of the company’s drugs mentioned earlier, can trigger a 24.2% weight loss. Eli Lilly is also researching Orforglipron, a tablet-based version of a GLP-1 receptor agonist, and Pfizer is also working on a GLP-1 pill called danuglipron.
Having snapped up pharma company Versanis Bio for $1.9 billion in 2023, Eli Lilly now also has access to their wonder-drug bimagrumab, which has been shown in trials to cause a 20.5% reduction in body fat – but also a 3.6% gain in lean muscle mass. Fat loss and muscle gain: imagine the internet appeal of that one.
These potent new weight-loss drugs are exciting and revolutionary, and they will help millions of people. But the lingering question is what happens when new drugs collide with age-old human nature. If we use them as a springboard for positive health change, humanity wins. But if we use them to perpetuate unhealthy habits, or if the drugs’ popularity undermines tough but necessary change to our toxically unhealthy modern lives, these drugs may only exacerbate the problems of obesity.
The wonder drugs are already here. What happens next is up to us.