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Exercise may help maintain weight loss after a person stops taking GLP-1 drugs. Image credit: Klaus Vedfelt/Getty Images.
  • There appears to be no need to stay on GLP-1 receptor agonist drugs used for weight reduction — such as Wegovy — forever if one accompanies their use with regular exercise, according to a new Danish study.
  • The medications, originally developed for diabetes, are becoming increasingly popular for weight loss, but until now, it seemed as if once a person started taking them, they had to take them forever to keep weight off.
  • The study found that people who combined such medications with exercise were more likely to maintain a weight loss of 10% a year compared to their starting weight after they had stopped taking the drugs.

The conventional wisdom regarding the class of effective new weight-loss drugs is that if one stops taking them, the lost weight will automatically return.

A new study from the University of Copenhagen and Hvidovre Hospital in Denmark finds that this is not necessarily the case.

The key, researchers find, is taking such medications while participating in a structured weight-loss program that extends beyond the use of the drugs.

Participants in the study maintained their weight loss up to a year after ending their medication treatment.

The new weight-loss drugs mimic glucagon-like peptide-1, GLP-1, which promotes a sense of satiety, and thus reduces the desire to overeat.

They release an agonist after a meal that travels to the brain, signaling fullness. It also slows down the emptying of stomach contents, reinforcing the sensation.

The new study appears in eClinicalMedicine.

These drugs have generally been developed for people with diabetes, with some being available for nearly 20 years. Only in the last few years have they become popular for weight loss. They are mostly injectable drugs, though the number of oral formulations is growing.

There are various GLP-1 medications on the market based on several compounds. Semaglutide is the drug known by the following brand names: Wegovy, Ozempic, and Rybelsus. Saxenda is a brand name for liraglutide, for example, while Trulicity contains dulaglutide.

Of semaglutide drugs, only Wegovy has received Food and Drug Administration (FDA) approval for the treatment of overweight or obesity in the United States. Of liraglutide drugs, only Saxenda has FDA approval as a weight-management treatment.

Other semaglutide and liraglutide drugs are used for weight management only in an off-label capacity.

The new study was a randomized, controlled trial conducted in Copenhagen, including 166 adults with obesity ranging from 18 to 65 years of age. The participants completed an 8-week calorie-reduction diet, achieving an average weight loss of 13.1 kilograms (kg).

At the end of this initial program, participants were randomly assigned to one of four groups for 52 weeks:

  • one group received a daily 3 milligram (mg) subcutaneous injection of Saxenda
  • one group received a placebo instead of Saxenda
  • one group was tasked with exercising without weight-loss medication
  • one group was given Saxenda and exercised regularly.

A year after they had stopped these treatments, 109 participants returned for weight assessments.

The researchers found that more of those who had received Saxenda and participated in regular exercise during the treatment phase maintained a 10% reduction in their initial body weight.

They were 4.2 times more likely to maintain their initial weightloss than those who had taken Saxenda without exercise during the treatment phase.

Of those who took liraglutide without exercise during the treatment phase, the average weight regain was 6 kg higher, compared to those who had received the combined treatment.

While GLP-1 medications have been with us for decades as diabetes drugs, some are hesitant to get started with them if they require a lifetime commitment — and expense — to maintain a significant weight loss.

As insurance coverage is currently uneven in the U.S., this study may bring comfort to such people.

The study’s senior author, Dr. Signe Sørensen Torekov, summed up her personal takeaway from the study, saying that “[i]t is actually possible to stop taking the medication without large weight regain if you follow a structured exercise regime.”

“Our study offers new hope as we have shown that the majority of those who take weight loss medication and exercise regularly are able to maintain the beneficial effects a year after treatment termination.”
— Dr. Signe Sørensen Torekov

While expressing concern about the low number of participants involved in the study, bariatric surgeon Dr. Mir Ali, who was not involved in this research, was nonetheless positive about its methodology and findings.

“I haven’t seen another study like this, so it’s a good start,” Dr. Ali told us.

While these medications have been viewed as nearly magical in their ability to help someone trim down, the study highlights that this is perhaps not the best way to view them.

“There are two ways I guess people are looking at this. One is, you know, they temporarily use the medication, get to a healthy weight, and hopefully, in that time period, they learn how to change your habits of eating and exercise and can maintain the weight loss,” said Dr. Ali.

The second perspective he cited involves a shift from looking at excess weight as being simply someone’s fault, and instead viewing it as a chronic disease, such as diabetes or high blood pressure. For some people, that means being on a medication in the long term, or for life.

”Agonists are very effective in obtaining healthy weight and reducing risk of cardiovascular disease,” pointed out Dr. Torekov. “Thus, depending on your age and co-morbidities, this is a good option for sustained healthy weight.

For weight loss, Dr. Ali noted, even exercise is no magic bullet all by itself.

“We tell our surgical patients exercise adds about 5 to 10% to the weight loss,” he said. Therefore, “Eighty to 90% of the weight loss is what you’re eating. So if you don’t make significant changes in your diet, nothing really works.”

“What we emphasize to our patients is reducing carbohydrates and sugars and sticking to protein and vegetables to force the body to burn fat,” added Dr. Ali.

Nonetheless, Dr. Torekov noted that “[a]ll people, regardless of body size, should perform exercise for improved or maintained health.”

As a bariatric surgeon, Dr. Ali also noted that these medications can help bring a person’s weight down to help make bariatric surgery safer. On the other side, he said, “[w]e have patients who have had surgery and maybe need to lose more weight and are struggling.”

Dr. Ali clearly explained of how GLP-1 medications should be viewed.

“I mean, we encourage all our patients, and we tell them the same thing: That the medications are a tool to help you change to a healthier lifestyle and diet,” he said. “Like any other tool, if you use it the right way, it works. If not, it doesn’t work.”