Why the long-term success of weight-loss drugs may depend on exercise

Why the long-term success of weight-loss drugs may depend on exercise

The new weight-loss drugs that suppress appetite and reduce food cravings can be quite effective at helping people drop pounds, with many losing at least 10 or 20 percent of their body weight while they take the medications.

But in the real world and despite the drugs’ effectiveness, as many as half of users quit the drugs within a year, studies show, because of their expense, side effects or for other reasons.

Afterward, the pounds almost invariably creep back, and, almost as worrying, the weight people regain tends to be almost exclusively fat, with little muscle. The result is that they are often metabolically less healthy than before they’d begun the drugs.

But an important, new, long-term study of people who used and then quit one of the weight-loss drugs suggests there may be a simple, accessible way to stave off unhealthy weight regain after stopping the drugs: exercise.

In the study, people who exercised while using a weight-loss drug kept off far more of their weight after quitting the medication than people who didn’t work out, and they maintained more muscle.

Signe Sørensen Torekov, a professor of biomedical sciences at the University of Copenhagen in Denmark and senior author of the new study, said the results strongly indicate that people using the drugs may be able to “preserve a healthy weight,” even after they quit the medication. “But they do need to do exercise.”

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Weight loss, with a catch

Most obesity experts agree that the holy grail of healthy, long-term weight loss is maintenance. Shedding pounds is possible for many people, in the short term. Keeping it off can seem almost impossible.

The new class of GLP-1 diabetes or weight-loss drugs, with brand names such as Ozempic, Wegovy, Zepbound and Mounjaro, seem to be intensifying that dynamic. GLP-1 is short for glucagon-like peptide 1 agonist; these drugs mimic the effects of the substance GLP-1.

Most people lose substantial weight rapidly on these drugs. But if they stop, the pounds typically return almost as quickly.

But is this rebound inevitable?

Torekov and her colleagues devised a multiyear, multipronged effort to find out.

It began with 195 Danish adults with obesity but no other major illnesses. They were put on an extremely low-calorie diet, under the supervision of the scientists, to rapidly lose about 30 pounds. Since this was to be a weight-maintenance study, the scientists wanted them to drop pounds fast, and then move to the maintenance phase.

For that phase, the researchers assigned some of the volunteers to start taking Saxenda, known generically as liraglutide, an early GLP-1 medication, to see if the drug would help them maintain and even augment their dieting weight loss. Saxenda is made by Novo Nordisk, the company that also makes two similar drugs – the diabetes drug Ozempic and the weight-loss drug Wegovy.

(The study was funded in part by the Novo Nordisk Foundation, a charitable organization affiliated with Saxenda’s maker. The pharmaceutical company itself had no oversight of the study or its results, a company spokesperson said.)

A separate group of volunteers started the same drug, but also a supervised exercise program, with twice-weekly, half-hour group spinning classes and 15 minutes of high-intensity, full-body resistance training, along with two at-home jogs or similar workouts. The exercise was mostly vigorous, meaning strenuous enough that people could barely talk while they were working out.

A control group didn’t exercise and received a placebo, instead of liraglutide. (Although the prescribing information for Saxenda says it should be used in conjunction with a low-calorie diet and increased physical activity, that recommendation is often ignored.)

After a year, almost everyone who took the drug had maintained the lower weight or lost more weight.

Those combining the drug and exercise had lost the most, though. They’d dropped about six pounds more than those on the drug alone, and more of those pounds consisted of fat, instead of muscle.

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What happened when they stopped the drug

The researchers published those results in 2021 in the New England Journal of Medicine. Then they began the most revelatory aspect of their study. They ended the medications and exercise sessions for everyone, leaving people to maintain – or regain – their weight-loss completely on their own.

After a year passed, the researchers invited all the volunteers back to the lab. One hundred and nine returned and researchers checked their body weight, body composition and current exercise habits.

For some, the year had been discouraging. Those who’d earlier taken the weight-loss drug without exercise regained about 70 percent or more of all the weight they’d lost since the start of the study. Most of these regained pounds were in the form of fat, not muscle, so they wound up with relatively higher percentages of body fat than before starting the drug.

“They’d gained weight in an unhealthy manner,” Torekov said.

But those who’d exercised while taking the drug had maintained considerably more of their weight-loss during this phase. Many remained at least 10 percent lighter than at the study’s start, and at least some of the weight they’d regained was muscle, leaving them with a healthier body composition than the other groups.

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Exercising just two hours a week

It’s easy to understand why the exercisers added fewer pounds after stopping the drug, Torekov said. “They were still exercising,” even without supervision or nudging from the scientists. According to questionnaires and activity trackers, they generally continued to work out for several hours a week, voluntarily.

These findings suggest “about two hours a week of vigorous exercise,” may be a good goal for staving off weight regain after ceasing a weight-loss drug, she continued. Mixing aerobic and resistance exercise is probably best.

Meanwhile, those who’d taken the drug without exercise were almost completely sedentary now, averaging fewer than 30 minutes of exercise a week.

“More of the ones who had not exercised while medicated had complained of fatigue” during treatment and afterward, Torekov said, which may have contributed to their inactivity now.

Overall, the results make a strong case for “the importance of adding exercise to a regimen that includes a GLP-1 medication,” said Daniel Drucker, a diabetes expert and senior investigator at the Lunenfeld-Tanenbaum Research Institute in Toronto, whose research helped pave the way for the GLP-1 drugs. He wasn’t involved with the new study.

“The results are very encouraging,” agreed Robert Kushner, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, who specializes in weight loss. “But further studies will need to be performed to see if a less intense exercise routine” has similar effects on weight maintenance when people stop a GLP-1 drug.

The study has other limitations. It used liraglutide, which is not as potent as more-recent obesity drugs. But “I would expect the results to be directionally similar with the newer GLP-1 drugs,” Drucker said.

It also involved relatively healthy Danes, who may not be typical of other people hoping to lose weight. And the study’s exercise routine wasn’t merely vigorous, which can be challenging. It was also free and closely supervised during the first year, a luxury unavailable to many of us.

Still, for now, the study tells us that to stave off weight regain and hold onto muscle during and after treatment with an obesity drug, “it’s really important you have an exercise program,” Torekov said.

Jerry David is a seasoned Senior Reporter specializing in consumer tech for BritishMags. He keeps a keen eye on the latest developments in the gadget arena, with a focus on major players like Apple, Samsung, Google, Amazon, and Sony, among others. Jerry David is often found testing and playing with the newest tech innovations. His portfolio includes informative how-to guides, product comparisons, and top picks. Before joining BritishMags, Jerry David served as the Senior Editor for Technology and E-Commerce at The Arena Group. He also held the role of Tech and Electronics Editor at CNN Underscored, where he launched the Gadgets vertical. Jerry David tech journey began as an Associate Tech Writer at Mashable, and he later founded NJTechReviews in 2010. A proud native of New Jersey, Jerry David earned his Bachelor of Arts in Media & Communication with honors, minoring in Innovation and Entrepreneurship from Muhlenberg College. Outside of work, he enjoys listening to Bruce Springsteen, indulging in Marvel and Star Wars content, and spending time with his family dogs, Georgia and Charlie.