By Liam Mannix
The cravings were gone. The “food noise”, once a cacophony inside her head, was silent. And the weight, for so long such a stubborn companion, just seemed to drain away.
Semaglutide changed Lauren Ash’s life, she says. The medication powers Ozempic (for diabetes) and Wegovy (for weight loss). Ash lost 35 kilos while on it. The burden on her arthritic joints eased. She found herself spending more time with her two daughters, just playing.
And then, after using the medication for 12 months, her pharmacist told her there was a worldwide shortage. And it all came back – the noise, the cravings, and then the weight.
Lauren Ash. After stopping semaglutide “everything just came back to the way it was. I got hungry again,” she said.Credit: Matt Turner
“Everything just came back to the way it was. I got hungry again,” Ash says. “And I gained it all back.”
Ash’s story illustrates what doctors see in clinics and scientists observe during clinical trials: when semaglutide treatment for weight loss stops, many patients regain the weight they have lost.
Studies generally suggest about two-thirds of the weight lost returns in the first year if the medicine is stopped abruptly.
That could change. Doctors are testing different approaches, like maintenance doses. But for now, many patients with clinical obesity face being on the drug for life.
“Our bodies are really good at protecting us from losing weight, even if we have extra weight to lose. These medications … counteract that response of the body to weight loss,” says Associate Professor Priya Sumithran, head of obesity medicine at Alfred Health. “When we stop taking them, we see the effect of that response.”
Lauren Ash at her business, Fancy That On Beach Road, in Christies Beach in Adelaide.Credit: Matt Turner
What happens when you stop?
Semaglutide appears to work by mimicking a human hormone, GLP-1, which is naturally released by the intestines after we eat. GLP-1 has a wide range of effects: in the brain, it signals fullness and decreases hunger, it slows our digestion, and it interferes with another hormone, glucagon, that causes food cravings.
Weight loss is caused because patients simply eat much less.
In a pivotal 2022 clinical trial, semaglutide caused patients to lose 17.3 per cent of their body weight on average over 17 months. After stopping the drug, they regained 11.6 per cent of their body weight over the next year.
Other studies come to similar conclusions, even if the patients take part in diet and exercise counselling.
Why?
Because our bodies have highly evolved mechanisms to protect us from weight-loss. When we gain weight, our brains seem to mark a new set point; when we lose weight, hormones are secreted to make us hungry.
“This is a survival mechanism,” says Associate Professor Niloufar Torkamani, head of medical weight management services at Austin Health.
“We’re supported to be living in a cave, eating fat, meat and berries. We are the survivors of famine and wars. Our bodies over years, with natural selection, have been designed in a way so we’re not supposed to lose weight.”
Some doctors worry this weight regain may pose its own risks, if it is all fat rather than a mix of fat and muscle. “Patients could be in a worse position after having weight loss and regain, as opposed to having maintained a certain weight,” says Dr Terri-Lynne South, chair of obesity management at the Royal Australian College of General Practitioners.
But there’s no hard scientific data to back that fear up yet, she cautions.
Indeed, that’s where many doctors are at: working in a space with more questions than answers.
Some clinicians are trying out micro-doses of semaglutide to try to hold patients at their goal weight. Others are trying a gradual weaning. Torkamani offers twice-yearly maintenance doses – but admits there’s no hard data to guide her, yet.
Nor is there hard data to show what risks lifetime semaglutide use poses, given we’ve only been giving the drug to people with obesity for a decade.
Meta-analyses suggest no increased risk of cancer or other diseases, although some, like pancreatic cancer, may be so rare longer follow-up data may be needed to reveal them.
In August, researchers in JAMA reported a potential signal for increased risks of suicidal thoughts – but other studies have come back with conflicting results.
“This type of medication has been used for the treatment of diabetes for nearly 20 years. There aren’t any new risks that have emerged over time,” said Priya Sumithran.
Lauren Ash, meanwhile, is back on a weight loss medication – this time Mounjaro, another drug that mimics the action of GLP-1.
“I think, for some people, it is a lifetime medication. But you need to be able to put those lifestyle changes into place as well. It isn’t a magic drug, you have to put the work in.”
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