How Ozempic works — and what happens if you stop taking it

Ozempic, a diabetes drug, isn’t officially approved for obesity, however doctors are permitted to prescribe it ‘off label' for weight management

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One of the effects of Ozempic, a diabetes drug that’s become a viral weight-loss sensation, is its ability to free up “brain space,” said Dr. Sean Wharton.

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“You hear people talking about it — ‘I’m so much happier now, because I’m free.’” Every minute of every day no longer preoccupied with thoughts about food — where to get it, how to get it, which drive-thru to hit on the way home from work and sneak food into the house and eat it before anybody notices. “Planning your day around food, that’s a lot of brain space,” said Wharton, an obesity medicine specialist and adjunct professor at McMaster University in Hamilton and York University in Toronto. “It’s frustrating, and exhausting.”

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When used for type 2 diabetes, Ozempic, the brand name for a drug called semaglutide, lowers blood-sugar levels. In people without diabetes, it helps control cravings and hunger and eating. In the field of obesity, Ozempic and its sister drug, Wegovy, are a “home run,” said Wharton, who has led drug-company sponsored studies of semaglutide. “I think it’s a breakthrough.”

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It’s also a forever drug: Once off, most of the lost weight returns.

Ozempic and Wegovy have become social media phenomenons. TikTok videos with a #ozempic hashtag have had 600 million views. In Canada, more than 3.5 million prescriptions worth nearly $1.2 billion were dispensed for Ozempic by retail drugstores in 2022, according to data provided to the National Post from IQVIA CompuSript. That’s up from just over 81,000 scripts worth $26 million in 2018, the year Health Canada approved the drug.

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Ozempic isn’t officially approved for obesity, however doctors are permitted to prescribe it “off label” for weight management. “While we cannot discern whether the (prescription) was written for diabetes or for off-label use, the growing numbers may reflect the potential for use as anti-obesity medication for long-term weight management,” IQVIA spokeswoman Madeline Gareau said in an email.

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Wegovy, which contains a slightly higher dose of semaglutide, was approved by Health Canada in November 2021 specifically for weight loss. Due to “unprecedented demand” in other countries, Denmark-based pharmaceutical giant Novo Nordisk has had to postpone Wegovy’s Canadian launch. The company said it’s working towards making the drug available in Canada, though it can’t yet confirm the timing.

Both Ozempic and Wegovy are once-weekly injections using pre-filled pens that are injected into bellies, thighs or arms.

The drugs have been touted by influencers, as well as tech billionaire Elon Musk. Who’s using, and who insists they’re not are all part of the gossipy Ozempic hype, along with reports of so-called Ozempic facial aging and muted alcohol cravings.

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How does semaglutide work, how safe is it and what does the Ozempic story say about biases toward larger bodies? The National Post spoke with Wharton and Ian Patton, a registered kinesiologist and director of advocacy and public engagement at Obesity Canada.

What is semaglutide, and how does it work?

Semaglutide is a glucagon-like petide-1 analogue, an unwieldy name for a drug also known as a GPL-1 receptor agonist. GPL-1 is an endogenous hormone, “meaning we make it ourselves after we eat food,” said Wharton, medical director of the Wharton Medical Clinic in Toronto.

It goes to the pancreas, to help the body produce insulin to regulate blood sugar levels.

But the messenger molecule also works on the brain to increase feelings of satiety, and, because the body still needs energy, it uses energy from the stored fat cells.

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“You can only lose weight by using up the stored energy, and you can only use up the stored energy consistently if you’re not hungry and you can feel full faster,” Wharton said.

Studies suggest the drug accesses areas of the brain involved in appetite regulation. A drug-company funded trial led by Wharton reported it can lower body weight and control cravings for salty and spicy food, or dairy or starchy foods, up to two years out.

The longer-term effects aren’t known. “The question now is going to be five, six, 10 years,” said Wharton. “How long can it last?”

Semaglutide has to be used in conjunction with a reduced calorie diet. It doesn’t melt fat, Wharton said. “It helps you eat properly. The drug helps you sustain caloric restriction on whichever diet you want to be on — keto, intermittent fasting, Mediterranean, or just plain old healthy eating.”

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Much of the recognition for semaglutide should go to a Canadian, Daniel Drucker, a University of Toronto endocrinologist who helped discover GLP-1.

How much weight can you lose on Ozempic?

In a trial involving nearly 2,000 adults published in the New England Journal of Medicine, people taking semaglutide lost, on average, 15 per cent of their body weight after 68 weeks of treatment, compared to 2.4 per cent for people in the placebo group.

The change in average body weight was 15.3 kg in the semaglutide group, versus 2.6 kg in the placebo. In a subgroup of people who underwent special X-ray imaging of their body composition, the semaglutide arm had less total fat mass and less visceral fat mass, the beer-belly fat that wraps around internal abdominal organs and increases the risk of type 2 diabetes and heart disease.

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Of course, not everyone responds. Treatment costs about $5,000 per year.

What are the side effects of Ozempic?

The drug slows the movement of food through the gut. Nausea and diarrhea are among the most commonly reported side effects, though they’re usually mild-to-moderate and subside with time.

Other side effects can include vomiting, constipation and stomach pain. Possible serious side effects can include inflammation of the pancreas or gallbladder or kidney problems. Ozempic has a boxed warning from Health Canada that semaglutide can cause thyroid tumours, including a certain kind of thyroid cancer, in rats and mice, but that it’s unknown whether it does the same in humans, “as human relevance could not be ruled out by clinical or nonclinical studies.” Health Canada says the drug should not be used by people with a personal or family history of thyroid cancer.

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More recently, The New York Times reports that some users are losing any desire for booze. “It’s certainly something that I’ve heard many of patients say, usually in a positive way,” Dr. Robert Gabbay, the chief scientific and medical officer of the American Diabetes Association, told the newspaper.

Billionaire Elon Musk, seen here in January 2023, has been a proponent of Ozempic.
Billionaire Elon Musk, seen here in January 2023, has been a proponent of Ozempic. Photo by Jonathan Ernst/Reuters

The belief, though not all the evidence is in, is that semaglutide works on the brain’s mesolimbic system, “the hedonic part of the brain, where you want more than what you need to sustain yourself,” Wharton said. The hedonic part of the brain is controlled by opioids, cannabinoids, and dopamine. Cravings live there, Wharton said. Cravings for food, alcohol and sex.

If semaglutide works by dialing down food cravings, theoretically it would stand to reason it could suppress other cravings as well, for some, but not all, people.

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There is no evidence it decreases sexual desire, Wharton said. “We have not seen that. When people feel healthier, and they have better self-esteem and more confidence, I believe that makes the sexual desire stronger.”

What happens when you stop taking Ozempic?

“You regain the weight,” Wharton said. “And you should, because of what obesity is.”

“I’m not talking about (someone) who is five pounds too high. People living with obesity — excess adipose tissue that’s causing disease — have a genetic condition that drives their eating behaviours.

“That genetic condition will never change. All this medication does is mask that genetic behaviour.”

In a study he helped co-author, researchers found that, one year after stopping their once-weekly semaglutide injections, people regained two-thirds of their prior weight loss.

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The findings “confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health,” the researchers wrote.

What is Ozempic face?

So-called Ozempic face “is a silly way of describing weight loss,” Wharton said.

As we get older, we lose the subcutaneous fat in our faces. “If you had excess weight, you may have fat in your face. You lose the weight; the face goes to where it would have been had you never had that excess weight in the first place,” Wharton said.

“It’s the same person the way they genetically would have been if their weight was lower.”

Older diet pill crazes like fen-phen had disastrous results. How can we know history won’t repeat?

The fenfluramine-plus-phentermine regimen was pulled from the market in 1997 after it was discovered the drug combo caused serious heart valve problems.

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Three years later, Merida, then a top-selling weight loss drug in Canada, was voluntarily withdrawn over an increased risk of heart attack, stroke and cardiovascular death.

“Is there going to be a problem 15 years from now, 30 years from now? I don’t know,” Wharton said. “But we’re not seeing any (safety) signals.” People need to understand their own individual risk-benefit ratio, he said. Semaglutide has been prescribed to millions of people with type 2 diabetes for 15 years “without any adverse effect profile,” Wharton said.

Is the TikTok celebrity buzz undermining body acceptance?

“Absolutely everybody should be able to live happy, healthy lives,” Patton said. “We should have body acceptance and body diversity.

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“But a lot of the time it turns into a dichotomy: you can’t have body acceptance, and also talk about effective obesity management for people who require it. And I think that’s wrong.”

People shouldn’t be pushed into any treatment that’s aimed at losing weight or changing their body, he said.

But the social media hype could also be taking away from what the drugs could mean for people with true obesity, he said.

Influencers trying to meet a certain body ideal “don’t really help us progress the narrative around obesity,” Patton said.

For more health news and content around diseases, conditions, wellness, healthy living, drugs, treatments and more, head to Healthing.ca – a member of the Postmedia Network.

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