Myth versus fact: What we know about the risks and side effects of the new weight-loss drugs

The Age

26-07-2025

Sofia had struggled with her weight since her early teens. A condition that upped fat levels in her blood made diets and exercise regimes futile. Lap-band surgery worked at first, but years later she regained much of the weight. So she didn't hesitate when Joe Proietto, her doctor and a former board member of the World Obesity Federation, suggested she try Ozempic. 'I felt that confidence in going on it,' she says.
When Proietto warned she might feel 'pretty rotten' to begin with, she thought little of it. On the first night, she gave herself the injection and settled into bed to watch TV. Suddenly, her stomach let out a gurgle. Within hours, she was in the grip of wave after wave of nausea. 'I was absolutely as sick as a dog,' she says. 'I had diarrhoea and vomiting for seven days straight. And I lost six kilos in one week.' In the second week, she adjusted to the medication. In the past six years, weight-loss drugs have helped her lose 25 kilograms. 'It just quietens your appetite,' she says. 'I know people who haven't been able to cope with the side effects and have stopped taking it but, for me, it was a short-term thing.'
Ozempic is part of a new wave of drugs, known as GLP-1 receptor agonists, that have evolved from treating diabetes to managing obesity and which are now in wider use for weight loss. Not only have they proven successful in helping people regulate blood-sugar levels and shed kilos (and in reducing weight-related issues such as heart conditions) but there is interest in their potential to treat other maladies, from Alzheimer's to addiction.
Unsurprisingly, the drugs are a hot topic of conversation – in the space where urban myth, anecdotal evidence and early scientific findings collide. How do you manage dinners where half the guests are barely eating? Do these drugs really 'eat' your muscles? What's 'Ozempic face'? What are the side effects? What happens if you stop taking them?
Where did the drugs come from (and what's a Gila monster)?
In the Sonoran Desert, in the south-west of the United States, a poisonous lizard feasts on rodents, birds and other reptiles to pack on fat – then stops eating for months. In the 1980s, venom from the Gila monster (pronounced 'hee-lah') caught the attention of US scientists, who observed it stimulating pancreatic cells harvested from guinea pigs. When they investigated why, they discovered a new peptide, which they named exendin-4.
As they looked closer, they noticed that exendin-4 was similar to a hormone in humans called GLP-1 – or glucagon-like peptide 1 – which regulates insulin, the hormone that controls glucose levels in the body and which causes us to feel full after eating. 'I used to tell the students that this hormone is released after a meal and then it does everything except wash the dishes,' says Joe Proietto, a professor emeritus at the University of Melbourne. 'It goes to the pancreas, binds to the receptor on the cells that make insulin and stimulates insulin release ... then [it] goes to the stomach and it slows its emptying, making you feel fuller for longer. And then it goes to the brain and suppresses hunger.'
People with diabetes produce less GLP-1. Until the Gila monster discovery, GLP-1 injected into humans stayed there for only a few minutes. But the peptide carried by the Gila monster lasted several hours. In 2005, US pharmaceutical giant Eli Lilly used it in the drug Byetta, for type 2 diabetes. 'I never imagined this peptide would have clinical importance or be marketed as a drug,' Jean-Pierre Raufman, one of the scientists who discovered the venom's importance, tells us from Washington DC. 'Sometimes being lucky is better than being smart.'
'I am very grateful that what started as a 'fishing expedition' turned out to be so impactful.'
As well as being effective for diabetes, Byetta led to people losing about 5 per cent of their body weight within months. It was proof of concept for Danish company Novo Nordisk to begin work on its own anti-diabetes drugs, which went on to mimic the naturally occurring GLP-1 with even longer-lasting results. (The drugs are called GLP-1 receptor agonists because they bind to and activate the body's GLP-1 receptor molecules.)
Raufman was surprised the pharmaceutical industry didn't catch on sooner to the potential 'marketability' of this new class of diabetes drugs for obesity. 'I am very grateful that what started as a 'fishing expedition' turned out to be so impactful,' he says.
Today, there are about half a dozen GLP-1 receptor agonists known by their active ingredients. In Novo Nordisk's latest drugs, this is semaglutide. It's found in Ozempic, available in Australia since 2019 as a weekly injection on the Pharmaceutical Benefits Scheme, along with a handful of other semaglutide drugs, for treating type 2 diabetes. Semaglutide is also in Novo Nordisk's Wegovy, available since late 2022 for treating obesity, although not on the PBS. Then there's the Eli Lilly drug, Mounjaro, with the active ingredient tirzepatide, which mimics both GLP-1 and a 'sibling' hormone called GIP – a combination that leads to greater appetite suppression.
The PBS recorded 2,397,521 prescriptions of semaglutide in 2023-24, up 60 per cent on the previous year (the figure includes individuals who have filled multiple scripts). In March, this jump prompted the federal Department of Health to send more than 1000 letters to doctors who had prescribed the drug through the PBS for weight loss, reminding them they can't do this for patients with no history of type 2 diabetes.
Doctors can prescribe Ozempic, Wegovy and Mounjaro 'off-label'. To whom? People with a body-mass index of 30 or more (which is considered obese); or with a BMI of 27 or more (25 to 29 is considered overweight) and who have obesity-related complications such as cardiovascular risk. A person's BMI is their weight divided by their height in metres squared.
But doctors will take other factors into account too, says Terri-Lynne South, chair of an obesity management group at the Royal Australian College of General Practitioners: whether they've tried these drugs before, their health literacy, fitness, mental health, any risks of eating disorders and their age. More research is needed into the drugs' effects on people over 65, she says, and older patients would need a particularly in-depth weighing of pros and cons before going on the drugs. (For one thing, muscle mass is already starting to decrease at that age.)
Off-label prescriptions don't have to be reported, so it's unclear how many Australians are taking the drugs. Without any PBS subsidy, they can be pricey: 'pens' of Ozempic cost $133, Wegovy $260 and Mounjaro $330 which, depending on the dose, can be a monthly outlay. 'The people who need these medications the most,' says South, 'are usually the ones who can afford it least, based on socioeconomic data.'
Do the drugs work (and what's food noise)?
Jen was in her mid-20s when she began putting on weight in what she now recognises as a food addiction. Her best friend owned a restaurant where she learned to like high-end food. 'You go from being a kid who is kind of happy with just what you have, until you understand you can have mushrooms that have been flown over from France and eat them the same day they arrive in the country,' she tells us. 'You procure stuff and do a massive cook-up and really enjoy things with a glass of wine and the music on, and have friends around. It was simple hedonism that got out of control.'
Over 15 years, she gained almost 100 kilos. She tried exercise and dieting to no lasting effect. When a tumour developed on her leg requiring surgery, doctors referred her to a weight-loss clinic with a team including a dietitian, psychologist, endocrinologist, exercise physiologist and sleep apnoea specialist. They suggested Jen try Ozempic.
Obesity is believed to be influenced by genetics, which can make it a stubborn challenge.
In 2023, on the first morning after taking the drug, she skipped breakfast without a thought. 'Usually by 10 o'clock in the morning, if I'm working from home and I don't manage to get breakfast straightaway, my stomach is rumbling and I'm dying – like, I could eat a truck driver's dinner.' She has since lost nearly 30 kilograms.
Obesity affects about a third of Australian adults, while another third is classified as overweight. There can be genetic differences between body types, sexes and racial backgrounds, so doctors often use waist circumference as another measure alongside BMI. As for what causes obesity, behaviour and environment play a role, yet between 40 and 70 per cent of obesity is believed to be influenced by genetics, which can make it a stubborn challenge.
Proietto and his colleagues have even found that when people lose just five kilograms, changes to the hormones that control hunger can make them feel hungrier – for several years. 'It was unbelievably frustrating treating obesity because everybody regained weight before long,' he says. 'Now, we've got tools – but we're still frustrated because of the high cost.'
The drugs cause weight loss by slowing gastric emptying, the movement of food from the stomach to the small intestine. The results have been game-changing. In 2021, Novo Nordisk's own clinical trials found people who took semaglutide lost 14.9 per cent of their body weight after 68 weeks, as compared with a placebo group who lost 2.4 per cent. Clinical trials from Eli Lilly's Mounjaro found it could reduce body weight by 25 per cent in the first year.
There are flow-on effects: some evidence of the drugs lowering heart attack and stroke risk, and reducing kidney disease. An Australian study in The Lancet that weighed up trials of several GLP-1 agonists (including semaglutide but not tirzepatide) found the drugs reduced the risk of kidney failure by 16 per cent.
'My friends will say, 'Is that all you're eating?' and I'm like, 'Yeah.' '
Colette McCracken, who lives in south-west Sydney, had tried diets, obesity support groups and a gastric sleeve (surgical removal of part of the stomach). She first used Ozempic in 2019 – and the results went far beyond her expectations. 'You can make good choices because you aren't so overly hungry,' she says. When McCracken goes out for dinner, she opts only for an entree. 'My friends will say, 'Is that all you're eating?' and I'm like, 'Yeah'.'
Another effect of the drug is it reduces 'food noise' – constant thoughts about food that might, for example, mean you're unable to walk into a service station without picking up a bag of chips, or the like. Jen describes the thoughts as relentless and intrusive: What are you going to make for dinner? Maybe you should go to the supermarket? What's on special this week? When it stopped, she experienced a new sense of calm.
'One woman who had alcoholic liver disease said, 'When I taste wine now, it tastes like vinegar.' '
How do the drugs silence thoughts? Katherine Samaras, an endocrinologist at St Vincent's Hospital in Sydney, says it's likely to be because GLP-1 receptors are also scattered throughout the brain. Researchers are still untangling how the drugs act on the brain more broadly. One area of interest is whether the medication has the potential to treat Alzheimer's disease after a London study of 200 people showed a semaglutide drug halved brain shrinkage in those with the disease and reduced cognitive decline by 18 per cent.
Addiction is another area of interest. One randomised control study of 127 people found the drugs didn't reduce heavy alcohol consumption. Still, Samaras and her colleagues have patients on the drugs who report reduced interest in alcohol. 'One woman who had alcoholic liver disease said, 'When I taste wine now, it tastes like vinegar.' She was having seven to eight standard drinks a day, minimum.'
What are the immediate side effects (and what's Ozempic face)?
A search on social media brings up anything from 'sulfur burps' (a rare side effect) to hair loss (which can happen during any rapid weight loss). Jen was anxious about side effects before taking Ozempic. 'I was Googling my head off,' she says. 'There was lots of stuff on social media, a lot of noise, and it was hard to get definitive information.'
The most common side effects of Ozempic are nausea, vomiting, diarrhoea, abdominal pain and constipation. Clinical trials by Novo Nordisk found about 20 per cent of people who take the drug experience nausea (although a small study of 150 people who'd taken it for two years found the number rose to more than half). The Therapeutic Goods Administration advises that, as of June 25, nausea, vomiting and diarrhoea are the common reactions they had received notice of, from 2046 reports. (The TGA encourages people to report even if there is only a very small chance that a drug caused an adverse event.)
As Proietto puts it: 'There is a huge range of sensitivity to the hormone.' Some people have the lowest dose and can't even look at food while others have the maximum and it doesn't work. Tailoring the dose is a process. Says Samaras: 'What really concerns me is that social media ... [is] promoting escalation of the dose when often you don't need to. By not escalating the dose and finding that individual sweet spot, you can actually mitigate or prevent the nausea.'
'The body, if you're crash dieting, will use up fat, but it will also use up fuels in the body like protein and so that's where people can get muscle wasting.'
Experts we spoke with said persisting through initial mild side effects might be necessary, but people shouldn't be suffering. Doses range between 0.25 and 2 milligrams for Ozempic and 2.4 milligrams for Wegovy. Doses of Mounjaro, which has a different potency, ranges between 2.5 and 15 milligrams. Proietto advises his most sensitive patients to start with a small dose of Ozempic, three clicks of the injection (a milligram is roughly 78 clicks), which he increases by one click a week, depending on the patient's tolerance. (Colette briefly had slight constipation when her dose increased but has had none since then.)
What of the ailment dubbed – mostly on social media – Ozempic face? Talk of it has coincided with a rise in online searches for face fillers and cosmetic surgeons to rectify it. Samaras explains this is not a direct side effect of the drug but rather a consequence of rapid weight loss. 'The body, if you're crash dieting, will use up fat, but it will also use up fuels in the body like protein and so that's where people can get muscle wasting or sarcopenia, and when you have that pronounced in the face, you'll lose muscle in the face.'
How should you eat on the drugs?
General practitioner Terri-Lynne South shows patients a chart of side effects to explain what they could expect before taking the drugs. 'If an individual is not tolerating them, I want them to come back to me and we'll be looking at, 'OK, well, why are you not tolerating them?''
A transition period is common as people change their eating habits to match their now-slower digestion. If they continue to overeat, it can contribute to nausea. South will initially tell people to put half as much as they usually would on their plate, and to take 15 to 30 minutes to eat each meal, even suggesting they set a timer and put down their knife and fork between mouthfuls. 'It's about pulling up at that first sign of feeling full.'
Dehydration is one sure way to make nausea worse; so is eating foods high in sugar, carbohydrates and fat, which naturally stay in the stomach for longer. 'So you've got the drug that causes that delayed emptying, and then if you add in foods that also stay around in the stomach, it's like a double whammy,' says South.
Constipation can be exacerbated by poor or unbalanced diets. Fibre and important fats such as oils help maintain bowel movements and prevent blockages. 'Some people use the medication in such a way that they don't eat, and if you don't have anything going through the intestinal tract, then there's not going to be a bowel motion,' Samaras explains. 'Some people don't have a balanced diet. They've just had a prescription for the medication. As you might see with some of the online pharmacies, there's no nutritional intervention, which is foundational to the appropriate use of these medications.'
'I have seen scurvy, which is vitamin C deficiency, when people just don't eat and their gums start bleeding.'
After days of using Ozempic, Jen thought to herself: You still have to eat but now are you going to do it smart? With a dietician, she developed a meal plan to ensure she eats 30 grams of protein a day to stop muscle wasting (up to a quarter of the weight that people lose can be lean body mass and muscle). Studies have found people who have a high-protein breakfast are also less likely to snack later. Jen's breakfast is usually two boiled eggs with spinach and tomatoes. Most days she has only one other meal such as soup, or poached chicken with vegetables, or a salad with tuna. If she needs a snack, she eats fruit or yoghurt.
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Two meals a day might work for some, for others it won't provide a balance between macronutrients (proteins and carbohydrates) and micronutrients (vitamins and minerals). Ideally, a daily diet includes 30 grams of fibre, 0.8 grams of protein per kilogram of body weight (adjusted for the healthy weight being aimed for), five vegetables and two pieces of fruit. Often it's about reducing fats rather than removing them – dicing lean beef for a stir-fry, for example, rather than cooking a marbled rib-eye. A lack of vitamin B12 can cause nerve damage and lower your ability to concentrate, a lack of calcium can affect bone density. Samaras refers patients who are new to the drugs for blood tests every three to six months to check their nutrition. 'I have seen scurvy, which is vitamin C deficiency, when people just don't eat and their gums start bleeding.'
She also gleans whether they should see a psychologist – 'you have to understand what makes people binge; is it when they're stressed?' – and an exercise physiologist. Anyone on a calorie-restrictive diet risks losing muscle mass and bone density. Alongside a diet with protein, resistance training two or three times a week helps offset this risk. Jen is up early most mornings to swim laps at her local pool. 'It's outdoor and it's freezing. Let me tell you, my Viking ancestors are proud of me.'
What do we know about long-term side effects?
A scroll through drug companies' disclaimers can be enough to raise anyone's heart rate. (As it happens, all GLP-1 receptor agonists generally increase heart rates by two to three beats a minute, which is not enough to cause damage.) The scarier risks listed for these drugs include thyroid tumours, pancreatitis (a potentially life-threatening inflammation of the pancreas) and vision loss. There's nothing unusual about drugs flagging potential long-term risks, especially when patient data is limited, says Katherine Samaras. 'We have this conundrum in almost every avenue of medical treatment. If we consider obesity a disease with mortality, comorbidities and life suffering then we need to balance up the risk versus the benefit.'
'If it does cause pancreatitis, it's extremely rare.'
What of pancreatitis? The TGA has received 358 reports of it since they started recording data on semaglutide in 2019, but whether these cases were induced by the drugs or are coincidental is unclear. The main causes of pancreatitis are wrapped up in common factors associated with weight gain, such as excessive alcohol consumption and gallstones. Novo Nordisk's two-year clinical trial of 3297 people on semaglutide showed nine had mild pancreatitis. Says Joe Proietto: 'If it does cause pancreatitis, it's extremely rare.' Still, he takes the precaution of starting people with a history of pancreatitis on a lower dose.
Then there's the eye condition called diabetic retinopathy that affects up to a third of diabetic Australians 50 or older. Novo Nordisk found 3 per cent of people in the two-year trial had subsequent damage to their retina. However, treating diabetes with too big of a dose of insulin is a well-known accelerant of retinopathy. In at least some cases, says Proietto, 'It's not the Ozempic that's doing it, it's the drop in sugar.'
Meanwhile, studies have found conflicting evidence for another eye condition – non-arteritic anterior ischemic optic neuropathy – which affects the optic nerve. Boston-based researchers found an 8.9 per cent incidence of this disease from studying 16,000 people prescribed semaglutide. Others have trawled a database of 66 million users and found no association. The TGA told us it was investigating. 'If a safety signal is confirmed, we will take regulatory action as appropriate.'
What about thyroid cancer? Novo Nordisk flags that semaglutide has caused what are known as C-cell tumours found in thyroid cancer during tests on rodents. In 2022, a study in France concluded there was an association between higher rates of thyroid cancer and people who used GLP-1 receptor agonists. Still, there's no causal link to use of the drug, says Proietto. 'And you know why? Because they found that monkeys and humans don't have receptors on them whereas rats do – our C-cells can't react to the GLP-1 because a hormone can't react unless it's got a receptor to bind to.'
This much is clear: people with bowel cancer should not use GLP-1 receptor agonists because the hormone can cause the cancer to grow. In other words, the drugs don't cause this cancer but can accelerate it. If any of Proietto's patients have a family history of the disease, he will explain the risks and let them make an informed decision. He points out there are other weight loss drugs that don't come with this risk, including Contrave, Phentermine and Xenical, because they don't use GLP-1 receptor agonists.
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What happens when you stop taking the drugs?
When Jen started on Ozempic in 2023 she would take it for a few months then not be able to buy it again due to widespread shortages at the time. With every interlude, she regained four or five kilograms, had to exercise more and would be back in the ring with her eating habits. 'It's a constant battle.'
In a 2021 trial funded by Novo Nordisk, patients regained two-thirds of their prior weight within 12 months of discontinuing their use of semaglutide. The see-sawing of people's weight has physicians concerned. 'It's expected when people lose weight they lose muscle and fat tissue,' says Terri-Lynne South. 'But we often see with the weight regain there's proportionally more fat gain, and it's the fat tissue that is the concern for the health risks.' In addition, the trial found associated conditions such as high blood pressure, type 2 diabetes or cardiovascular risks return after people stopped taking semaglutide.
'Not taking the medicine and then taking it again is like chalk and cheese.'
However, anecdotes about what happens to people's weight when they stop are mixed. Not everyone regains substantial weight, says Samaras. 'My view is that's because there has been the support to keep people on track with psychological support, nutritional support and the championing and encouragement of people to stay on this narrow pathway.' She has seen her patients go off the drug without regaining so much as half a kilogram. 'They say, 'I was too scared to go back to eating the way I did. I ate exactly as I did when I had the medication'.'
Without the drug, Jen notices aches – a return of inflammation from overloaded joints. 'Within a week, everything starts to hurt again when you get out of bed,' she says. 'Not taking the medicine and then taking it again is like chalk and cheese.' Samaras says when people restrict their calories, they reduce immune cells that cause inflammation by 80 per cent – therefore, if they go off the drug their inflammation can return.
Then there are those costs. Each time Jen stops and restarts Ozempic she notices she needs a higher dose 'to then maintain that same equilibrium'. She recently switched to Mounjaro, at $565 every two months. 'You have to be committed because, like, I could do three pens and be in Fiji for two weeks eating lobster, right?'
Still, the medication has put a healthier life within her reach. 'My goal is not about aesthetics,' she says. 'It's actually just being strong for longevity, and I'm not waiting for a written invitation for a heart attack, a stroke, diabetes or any other fat-related disease.'