Drugs that induce rapid weight loss, like Ozempic and Wegovy, are some of the most talked about medications on the market today. Yet despite recently exploding in popularity, some researchers are skeptical of their long-term benefits.

Studies suggest that once a person stops the weekly appetite-suppressing injections they typically regain about two-thirds of lost weight within a year.

That doesn't have to be the reality. A randomized controlled trial, led by experts at the University of Copenhagen in Denmark, has found a solution.

When patients combine liraglutide injections with a supervised exercise program they maintain their weight loss much better a year after the drugs and supervised exercise are stopped, researchers say.

Liraglutide is different to the drug behind Ozempic and Wegovy, which is called semaglutide. Both medications, however, belong to a branch of pharmaceuticals known as glucagon-like peptide-1 (GLP-1) receptor agonists. These drugs work by mimicking a natural hormone in the body that controls blood sugar, and they were initially designed to treat diabetes.

Today, researchers are still figuring out how to best use the appetite-suppressing nature of these drugs for controlled weight loss.

"Even though medical treatment for obesity is effective, people who stop taking the drugs have difficulties maintaining the beneficial effects," explains biomedical scientist Simon Birk Kjær Jensen from the University of Copenhagen.

"However, our study shows that people who exercise during treatment do not have the same propensity to put on weight post treatment."

The clinical trial in Denmark is the first to directly compare body weight changes after physical exercise, as opposed to pharmaceutical interventions, or both treatments combined.

The trial involved 109 adults with obesity, who were randomly split into four groups. One group undertook a year-long weight loss plan that included liraglutide injections only. Another group was assigned liraglutide and moderate-to-vigorous exercise that was supervised for two hours a week. A third group underwent only supervised exercise. And the last group underwent no specific weight loss plan.

A year after the end of the trial, researchers checked up on all of the participants to see how they were managing their weight on their own. Those who had taken liraglutide had regained about two-thirds of their initial weight loss. Those prescribed only exercise fared better in the long run.

The findings reveal that while liraglutide can result in weight losses comparable to exercise on its own, the drug is not as effective at maintaining weight loss as exercise on its own, the researchers conclude.

In fact, a year post-treatment, those who started and stopped liraglutide regained roughly 6 kilograms (13 pounds) more than patients who underwent a supervised exercise regime for a year.

The only participants to show better outcomes than those in the exercise-only group were those who underwent combined treatments. A substantial number of patients who combined liraglutide with supervised exercise were able to sustain a weight loss of at least 10 percent of their initial weight a year after stopping treatment.

On average, they weighed about 5 kilograms less than those in the liraglutide-only group a year post-treatment.

This difference was due not only to greater weight loss during active treatment, but also to reduced weight gain once treatment had ceased.

The sustained outcomes are probably due to participants picking up healthy exercise habits and maintaining those habits even without supervision, researchers say.

While GLP-1 receptor drugs can trigger an initial loss of weight, they don't change a participant's lifestyle, and they can come with a bunch of unfortunate side effects that could actually make exercise less appealing.

"From our data, it is clear that those who followed an exercise regime with or without treatment with obesity drugs felt less tired and more energetic. They also experienced better mental health. It simply led to improved quality of life," says biomedical researcher Signe Sørensen Torekov.

"The same did not apply to those who only received medical treatment. In fact, they felt more tired and less energetic."

"The study almost makes me want to advise against medical treatment without increased physical exercise, especially if you do not want to be taking the drugs for the rest of your life," adds Sørensen Torekov.

More research needs to be done on larger cohorts to really explore how weight-loss drugs like liraglutide can be used most effectively for long-term maintenance of body weight.

Despite all the hype surrounding these appetite suppressing drugs, exercise is a prescription that isn't likely to be replaced anytime soon.

The study was published in LANCET eClinicalMedicine.