Emma was at the point of trying anything. She was 49, and 98kg. Her weight had been rising for years. She couldn’t run any more – an activity she’d enjoyed – and her joints were painful. Her doctor had told her she was prediabetic.
Emma (not her real name) is an Auckland-based marketing manager and says she has a healthy relationship with her body, but she also feels the societal pressure of being a larger woman.
“It’s okay to be older if you are slimmer,” she says.
She has noticed this particularly in a work context. “I think if you are an older, overweight woman, you’re just throwing up another hurdle, another barrier in front of yourself. From a business and career perspective, [I feel] I need to be smaller, because my perception is that being an older, overweight woman with grey hair is just too many marks against you.”
Emma has worked hard on her health, and on weight loss. “I exercise. I go to the gym four days a week. I don’t drink lots. I don’t smoke. I don’t eat crappy foods,” she stresses. Even after seeking the help of a dietitian, she lost just 2kg in 12 weeks. “The dietitian said, ‘You’re doing everything right.’ I don’t know what to do next.”
What Emma did next was talk to her doctor about medications. And that led her to the new frontier in weight loss: GLP-1 agonists. More commonly recognised by their brand names such as Ozempic, Wegovy and Saxenda, these are the blockbuster drugs made famous by such celebrities as Oprah Winfrey and Elon Musk. They’re the reason many in Hollywood have apparently shrunk their already-small bodies dramatically.
This new class of drugs was first released in 2005 for the control of type 2 diabetes. For that condition, they offered an “absolute game changer”, according to endocrinologist and diabetes specialist Jeremy Krebs, a professor at the University of Otago, Wellington, and part of the Edgar Diabetes and Obesity Research Centre. Krebs and his colleagues were involved in some of the early trials of GLP-1 agonists for diabetes.
“I’ve been around a bit too long now,” he says with a smile, “and I’ve seen four or five new classes of drugs come in over the course of my practising time in diabetes. And I think the GLP-1 agonists are probably the most important additional drug class in the armoury of managing diabetes and obesity that I’ve seen.”
As people with diabetes using GLP-1 agonists started to experience weight loss alongside other better health outcomes, versions of the drugs were quickly developed and released under different brand names to treat obesity on its own. The doses needed for weight loss are generally larger than what’s used for diabetes.
GLP-1 agonists work by boosting the action of a gut hormone called glucagon-like peptide-1 (GLP-1). The lower small intestine produces this peptide after eating, when it stimulates insulin release. It also reduces the counter hormone to insulin, glucagon.
“They’re push-me-pull-you hormones,” Krebs explains, “so it’s one biological action, if you like … and that has a direct effect on glucose metabolism and on the liver hand-ling of glucose.”
As well as boosting insulin production, the drugs affect the appetite and satiety centre in the brain – the hypothalamus – making users feel full and signalling the stomach to slow down gastric emptying.
“So, as I say to patients,” Krebs says, “it gives the body more of a chance to process the food they’ve eaten.”
The effect can often mean a quieting of what many users describe as “food noise” – the preoccupation with and desire for food.
“Obviously, from a weight point of view, if it’s promoting satiety and reducing energy intake, that’s going to be effective.”
Hugely effective, as it turns out. Trials of the drugs have shown participants losing 15% of their body weight or more – equivalent to the results seen in bariatric surgery. It’s “quite astonishing”, says Krebs, and far greater than the results seen with any previous weight-loss drugs.
Supply shortages
It didn’t take long for the buzz to hit Aotearoa. While Hollywood favourite Ozempic was approved here for diabetes (but not weight loss) early last year, global supply shortages mean it is yet to arrive on our shores.
In fact, getting hold of the same kinds of weight-loss drugs here takes dedication and lots of cash.
For diabetes, similar drugs are available, though with limitations. GLP-1 agonists Trulicity (dulaglutide) and Victoza (liraglutide) are funded for diabetes treatment, but can also be used off-label for weight loss, if you don’t mind paying hundreds per month. But these drugs are also in short supply and Pharmac has limited funded access for 2024 and 2025 to people already taking them.
What is available with no current shortages is Saxenda, a version of liraglutide designed for weight loss; it’s the one Emma was prescribed. The drug is injected daily. It’s unfunded and the cost is $500 a month.
It was a cost Emma was prepared to pay initially. She could afford it, just. And the promise of the medication seemed worth it, with examples she was seeing in Facebook support groups, such as one from an anonymous poster who reported she was down from 190kg to 145kg. “If someone had said to me this time last year I could lose 45.9kg in seven months, I’d have laughed in their face,” she wrote.
Emma is not alone in seeking the support of medication. Demand for these drugs has exploded so much that pharmaceutical market analysts are predicting GLP-1 agonists will become the bestselling drug class globally by the end of this year. The impact of celebrity and influencer endorsement is openly acknowledged; this is also the reason there are now massive worldwide shortages of most of the medications.
As in most countries, obesity has been on the rise here for years. According to the most recent NZ Health Survey data, about one in three adults and one in eight children are classified as obese. A further one in three adults are overweight. As is the case with many other diseases, people in the most deprived communities are far more likely to suffer.
A magic pill?
UK-based Scottish journalist Johann Hari has been on Ozempic for 11/2 years. He’s lost 19kg and moved himself from the obese to normal weight range. In his book, Magic Pill: The Extraordinary Benefits and Disturbing Risks of the New Weight-Loss Drugs, Hari takes a deep dive into these drugs and their impact not only on individuals, but also on the wider world and culture.
He also documents his own struggles with binge eating and poor body image – something he’s lived with since childhood – and the moral and psychological challenges that taking these medications present.
He describes the “moment of madness” the world has reached, where the global food system seems designed to make us unhealthy. How, he asks, can the only solution be to create a drug?
“We built a food system that poisons us,” he writes, “and then, to keep us away from the avalanche of bad food, we decided to inject ourselves with a different potential poison, one that puts us off all food.”
In his book, Hari investigates some of the well-known systemic issues driving obesity, tracking the rapid cultural and societal changes that have sent rates hurtling up along with the many biological, psychological and social drivers of obesity at an individual level.
Krebs is well aware of our obesogenic environment. Echoing Emma’s grim assessment, he reckons there’s also a pervasive societal view that obesity is a personal failure. “You can develop a cancer and, gosh, that’s tragic and bad luck and poor you,” he says. “But you develop obesity and there’s still this pervasive judgment that it’s somehow your fault, your moral failing.
“And yet, the more we learn about obesity, the more we understand that the genetics are powerful. If you happen to unfortunately inherit those genetics and are put into our world, our built environment and our food environment, then you haven’t got a hope in hell of not gaining weight.”
Weight stigma is something Hari also explores. He notes the complex and as-yet-unresolved interaction between the body-acceptance and Health at Every Size movements – which have gained momentum in recent years and are much needed in the fight against weight stigma – and the fact that obesity is an acknowledged risk factor in a range of diseases.
The new drugs have been criticised by body-acceptance advocates as a step backwards for fat acceptance. “The Ozempic moment neatly lays bare exactly how much our society still hates fatness and fat people, and the extreme measures people who are already physically healthy are willing to put themselves through to be just that much leaner,” wrote Rachel Pick in the Guardian.
In the US, clinics promoting the new drugs are now using plus-size influencers to help market their services, causing controversy in the fat-activism community.
Complicated feelings
In the process of his own weight loss, Hari has had to confront the uncomfortable truth that what was driving his eating behaviour was not straightforward, and not simply that he enjoyed KFC too much.
“It was really strange,” he remembers. “The first six months I was taking the drugs, I was getting what I wanted, right? I’d lost loads of weight, my back pain went away. I was sleeping better. I could feel that I was physically fitter. Loads of great things happened. My neighbour’s hot gardener hit on me.
“But weirdly, I didn’t feel better emotionally. I wasn’t depressed or anything, but I didn’t feel better.”
Hari describes an incident around this time. Feeling sad and stressed, he turned to his familiar comfort: fried chicken. At a KFC outlet he ordered on autopilot. But the food was no longer comforting.
“I sat there and I had one chicken drumstick and I suddenly thought, ‘Oh, I can’t eat this.’ You can’t overeat when you’re on these drugs.
“You know those moments when you have an insight and you almost hear it like a voice in your head? I remember thinking, ‘Oh, you’re just gonna have to feel bad, then.’”
Hari says it’s a good thing the drug disrupted his underlying eating habits. “But what that can also do is bring to the surface some of the deep, underlying psychological reasons you eat in the first place. Now, again, that can be a good thing. There are clearly better ways for me to deal with sadness than stuffing myself. But I don’t think people are really prepared for that. If your relationship with food profoundly changes and you have to build a new relationship with food … that can be a bumpy and difficult process for many people. And I was surprised by how much it was for me.”
Side effects
Some of the other side effects of the new drugs are more visceral. Krebs explains that the most common are gut related, most often upper gastrointestinal tract issues such as nausea and vomiting. User support groups on social media are peppered with people suffering more severe issues, though; there’s talk of debilitating gut pain, constipation and what users euphemistically call “sulphur burps”. This was something Emma experienced, alongside chronic nausea and what she describes as “urgent, violent, explodey diarrhoea”.
Other known serious issues include the potential higher risk of pancreatitis and types of thyroid cancer. And in rare cases, the slowdown in gastric emptying – so useful in creating satiety – can go too far and cause gastroparesis, or stomach paralysis.
There’s debate in scientific circles whether GLP-1 agonists may be causing dangerous mental health symptoms such as depression and suicidal ideation in some patients; there are anecdotal reports of this, but the jury is still out. Some of the drugs’ packaging carries warnings about potential mood symptoms.
It’s an example of a point many experts make, as does Hari, about the unknown unknowns. He writes that the world has embraced these drugs “knowing surprisingly little about them. We have no idea of their long-term effects when they are used to treat obesity”.
It’s an important question mark, given these drugs need to be used long term for their benefits to be sustained. To keep the weight off probably requires a lifetime commitment, as with other drugs used for chronic conditions.
Krebs explains this to his patients using the analogy of hypertension. “You don’t expect to go onto a drug to treat your blood pressure for two years, come off it and then expect your blood pressure to be suddenly normalised. It’s not like that. And this is exactly the same. It’s biology we’re working against. It’s not someone’s inability to resist the chocolate biscuit. So, unfortunately, it really does look like there’s a need for ongoing usage over time.”
One possible positive signal is that GLP-1 agonist drugs have been used in patients with diabetes for more than a decade and, so far, the benefit-risk equation is tipping in their favour.
“All the clinical trials have shown that the GLP-1 agonists are associated with really significant reductions in risk of cardiovascular disease, of stroke, of diabetes-related kidney disease, et cetera,” says Krebs. “So the health impact over and above the weight loss is really quite phenomenal.”
Another unknown is whether patients may develop tolerance to the drugs over time and see weight regained. Krebs says this can happen with bariatric surgery, to a degree, but weight tends to stabilise in the long term. He suspects these drugs may produce similar results, but time will tell.
Hari accepts the fact that he’ll likely be on Ozempic long term. With his family history of heart disease and his personal history of obesity, the benefits outweigh the risks for him. Others, he reckons, will make a different decision. “People have said, ‘I loved your book. It made me absolutely convinced I should take these drugs.’ And some other people have said, ‘I loved your book. It convinced me I’d be insane to take these drugs.’ Which is probably about right.”
For Emma, the side effects and the cost of the medication outweighed the benefits she saw. Though she lost several kilos over three months, the prospect of spending $6000 a year for decades on top of feeling terrible was too much.
“I know people who are doing really well on it. But for me, I just thought, I need to do something that works for me for the rest of my life. And this is not sustainable.” She’s booked in for bariatric surgery.
Big pharma scrambling
New and even more sophisticated weight-loss drugs, which work on multiple biological pathways at once, are on the horizon. And drug companies that don’t have a player in this class are scrambling to develop one. Diabetes drug Victoza (funded for use here) and its weight-loss partner Saxenda recently came off patent, meaning other companies can now work on developing generic equivalents. This might mean the cost and availability of the drugs improve, especially in countries like New Zealand, which tend to be at the bottom of drug companies’ supply lists.
In an ideal future, Krebs would like to see these drugs funded and available on prescription to those with obesity as well as diabetics.
Hari’s vision is even broader – one where “unless one of the risks turns out to be worse than we think – and I don’t rule that out at all – I predict more than half the population in New Zealand will be [using these drugs] 10 or 20 years from now, with huge implications for the economy, for society and for health, for better and for worse.”