Long-term medication or modern crash diet? Inside the new world of GLP-1s

At a bridal shop in downtown Halifax, Beverley Smith is trying on wedding dresses, but there’s a catch: She's rapidly losing weight since starting a GLP-1.

The 32-year-old has already gone on and off several types of these popular medications to manage weight gain and other side-effects linked to polyendocrine metabolic ovarian syndrome (PMOS), but decided to get serious about her health before getting married next summer. 

She’s lost more than 30 pounds since starting the drug tirzepatide back in March, and says related symptoms — like joint pain — have improved as well.

Now she’s asking the same question as millions of GLP-1 users around the world: Is it possible to one day stop taking the drug that’s changed life for the better?

"When you are going off it…. do you taper off of it or do you stop abruptly?" Smith wondered. "What is this really going to look like in the long term?"

As these blockbuster drugs explode in popularity, with more people using them off-label for short-term weight loss, scientists are also striving to find an answer.

"This is a real-world situation that needs to be studied," said Dr. Thomas Leung, a clinician-scientist at the University of Pennsylvania, who’s among the researchers doing exactly that.

Microdosing, drug cycling and more

GLP-1 drugs work by suppressing blood sugar, controlling appetite and slowing stomach emptying, all by mimicking their namesake hormone, glucagon-like peptide-1, which is released after you eat. 

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While these medications only became part of the zeitgeist in the last few years — driven by celebrity endorsements, before hitting the mainstream — they’ve been around for more than two decades.

The earliest forms were studied and approved to treat Type 2 diabetes. Later, options arrived for chronic weight management. What’s relatively new is the myriad ways people are using these medications, often with minimal medical supervision.

At a private appointment inside Kind Bridal in Halifax, Beverley Smith tries on a wedding dress and discusses alterations to accommodate her ongoing weight loss while using a GLP-1. (Hugo Levesque/CBC)

Many patients — or as some drugmakers now call them, "customers" — are treating GLP-1s like a yo-yo diet rather than taking them long term to manage chronic health conditions.

They’re ever easier to get through online pharmacies. And pill forms, versus injections, are becoming more accessible. (Though not yet available in Canada, there is a pill-based form of semaglutide — the drug best known by the brand name Ozempic — already approved in the U.S. from drugmaker Novo Nordisk, alongside a pill version of orforglipron from Eli Lilly.)

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Scroll through social media and it’s easy to find a range of short-term uses, from bodybuilders cycling through different types of GLP-1s (and steroids, too) alongside their gym routines to women "microdosing" the drugs off and on to manage menopausal weight gain to brides and grooms doing quick stints to lose weight before their wedding day.

One recent study from a Danish research team looked at the use of semaglutide for obesity and found roughly half of adults stopped treatment within just 12 months.

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Stop-and-start approach could hinder weight loss

It’s a trend Dr. Leung, the researcher from the University of Pennsylvania, noticed in his own social circle in recent years, as more of his friends and colleagues wanted to try GLP-1s just to drop a few pounds. 

Some talked about wanting to shed weight before a vacation or to look good on Instagram or just to feel healthier. The common thread? A desire to go on the meds, then get off them as fast as possible. 

"No one had really studied what happens when you model what human behaviour is, which is starting and stopping these drugs," Leung said. "So we’re like, OK, well, obviously you can’t test this in humans. But we can try to do this in mice."

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Leung and his research team did exactly that, and found cycling overweight mice through GLP-1 use seemed to make the drugs less effective over time. Mice who started and stopped the drugs every two weeks struggled to lose weight compared to mice who stayed on GLP-1s for the entire months-long study. 

Even after two months of consistent use at the end of the study period, the drug-cycling group remained 20 per cent heavier.

If that was happening to mice, Leung started to wonder: What’s actually happening inside the bodies of human patients stopping and starting these body-changing drugs?

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'Buyer beware' when using GLP-1s off-label

Dr. Sean Wharton sees that regularly in his own patients at the Wharton Medical Clinic for weight and diabetes management in Burlington, Ont.

"People are using it off-label often. Maybe they heard about something on the internet or on Facebook. And if they're using it in this manner off-label, then it’s … buyer beware," he said.

"Because I don't know what type of negative aspects could potentially happen. There could be mainly positive and no negative aspects, but we don't exactly know yet."

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Wharton stressed this growing class of drugs has clear benefits as a long-term treatment for obesity, which has a dangerous domino effect on other health issues, like inflammation and cardiovascular disease, when left untreated. 

Research also suggests GLP-1s may help curb substance use disorders, cut the severity of sleep apnea or even reduce cancer risk. 

Dr. Sean Wharton is an internal medicine specialist and clinical researcher in obesity medicine in Toronto. (Craig Chivers/CBC)

Yet increasingly, these drugs are moving from tested treatment into what Wharton calls the "aesthetic medicine space" for short-term use. And he says the benefits likely vanish when patients rush back off these drugs. 

"If losing the weight was the reason why your metabolic condition — like your heart failure, your high blood pressure — got better, then regaining the weight usually means that that blood pressure is going to go back up."

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Last year, one major research review concluded that the "magnitude and consistency" of these kinds of health effects "underscore the physiological consequences of [GLP-1] discontinuation." 

A key need, according to that research team, was treatment guidelines to also address how to stop using the drugs.

What's the best way to go off these drugs?

GLP-1 pioneer Dr. Daniel Drucker agrees with that approach. In Toronto, he’s helping lead a randomized controlled trial — the gold standard of health-care research — to find out the best way for people to safely stop taking the drugs that he helped bring to the masses.

The research team, which includes Wharton and Drucker’s colleague and fellow endocrinologist Dr. Caroline Kramer, is recruiting patients for a 16-week-long study period where they’ll go through regular bloodwork and other metrics to gauge the impact of slowly tapering off a GLP-1 compared to abruptly stopping. 

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"We’re trying to answer a very simple question: If someone wants to know, can they come off the GLP-1 medicines, what is the best way to do it?" Drucker told CBC News inside a lab at Mount Sinai Hospital.

"Pharmaceutical companies are not good at studying how to stop their medicine," Drucker said, "but we need to answer that question."

GLP-1 researchers Dr. Caroline Kramer, left, and Dr. Daniel Drucker are studying the best way to stop using these blockbuster drugs through a trial based out of Mount Sinai Hospital in Toronto. (Lauren Pelley/CBC)

Drucker is among those who sees huge potential for GLP-1s as a way to reduce the dire impacts of obesity — a public health crisis so widespread that just this year, the World Health Organization released its first-ever guidelines to manage obesity starting from childhood.

But tackling long-term medical issues usually requires long-term treatment, he stressed. When you discontinue minoxidil for hair regrowth, for example, hair loss restarts. If you suddenly stop taking statins, cholesterol spikes fast. Why would GLP-1s be any different?

"There is a lot of stigma around staying on a medicine to control your body weight for long periods of time, but we would never have anyone question if they had MS or Crohn's or hypertension or high cholesterol," Drucker said.

"I could list at least 125 diseases where you take the medication for the rest of your life to control the disease, but for some reason with the GLP-1 medicine, people think, well, you should be able to do this yourself."

Short-term use may 'cause more harm than good'

Kramer said there really hasn’t been research to help show if the cardiovascular benefits of being on a GLP-1 can be maintained by gradually tapering off rather than quickly stopping. 

The team will also be watching for symptoms and adverse events, given there can be a range of side-effects from common stomach upset to acute pancreatitis to rare reports of vision loss.

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Kramer's advice for Canadians who want to do a short-term stint on a weight-loss drug before her team’s results come in? 

"Patients who want to shed, like, three pounds because, ‘I have a wedding in two weeks’ … that is not what the medications were meant for," she said. 

"If you are thinking of taking a medication without the proper assessment over a short term … it may cause more harm than good."