Patients cycling off GLP-1 drugs risk diminished effects, researchers warn
Researchers say starting and stopping popular weight-loss drugs may make them less effective over time.
HALIFAX · A Halifax bride-to-be who has lost more than 30 pounds using a GLP-1 drug is among millions of users wondering if they can ever stop taking the medication. Beverley Smith, 32, began taking tirzepatide in March to manage weight gain linked to polyendocrine metabolic ovarian syndrome ahead of her wedding next summer. She says her joint pain has improved, but she is unsure about the long-term plan. "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, scientists are striving to find an answer.
Dr. Thomas Leung, a clinician-scientist at the University of Pennsylvania, is studying what happens when people start and stop GLP-1 drugs. He noticed a trend among friends and colleagues who wanted to try the medications to drop a few pounds for a vacation or to look good on social media, then stop quickly. "No one had really studied what happens when you model what human behaviour is, which is starting and stopping these drugs," Leung said. His research team tested the pattern in mice, cycling overweight mice on and off GLP-1 drugs every two weeks. They found those mice struggled to lose weight compared to mice who stayed on the drugs, and remained 20 per cent heavier even after two months of consistent use at the end of the study.
GLP-1 drugs work by suppressing blood sugar, controlling appetite and slowing stomach emptying. While originally approved for Type 2 diabetes and later for chronic weight management, they are now often used off-label for short-term weight loss with minimal medical supervision. They are increasingly easy to get through online pharmacies, and pill forms are becoming more accessible. Social media shows a range of short-term uses, from bodybuilders cycling through different types to brides and grooms using them briefly before their wedding day. A recent Danish study found roughly half of adults stopped treatment with semaglutide for obesity within 12 months.
Dr. Sean Wharton, an internal medicine specialist at the Wharton Medical Clinic for weight and diabetes management in Burlington, Ont., sees patients using the drugs off-label regularly. "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." Wharton stressed the drugs have clear benefits as a long-term treatment for obesity, which can worsen other health issues like inflammation and cardiovascular disease. Research also suggests GLP-1s may help curb substance use disorders, reduce sleep apnea severity or lower cancer risk.
Yet Wharton says the drugs are increasingly moving into what he calls the "aesthetic medicine space" for short-term use, and the benefits likely vanish when patients stop. "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." A major research review last year concluded that the magnitude and consistency of these kinds of health effects show the physiological consequences of GLP-1 discontinuation. That research team said a key need was treatment guidelines to also address how to stop using the drugs. Health Canada has approved the first generic version of Novo Nordisk's Ozempic and has warned about fake or unauthorized versions of GLP-1 drugs.
With files from CBC News
Amara Okafor covers health, medical research and public health in Canada for Novello Desserts.