Weight Loss Drugs Combined With Exercise Helps Patients Maintain a Lower Weight Over Time, New Research Shows

Prescription weight loss medications have quickly caught on as a beneficial tool for combating obesity in the United States. Millions of Americans have successfully lost weight while using GLP-1 medicines. And the number of patients using injectable semaglutide medicines like Ozempic and Wegovy has increased 40-fold in the last five years, according to electronic health records data Epic Research shared with CNN. 

However, dropping the pounds is just the beginning. Maintaining a lower weight has proven exceedingly tricky for many people. Data shows a significant amount of patients regain some, or even all, of their pretreatment weight after discontinuing medication.

A new study shows a more comprehensive, holistic approach to weight loss may be the solution. Researchers in Denmark found that when weight loss medications are combined with exercise, patients are better able to maintain a lower weight. 

Researchers recruited adults with obesity but no serious chronic illnesses for the study. Participants followed a low-calorie diet for eight weeks to help them drop weight fast and then they moved on to the year-long controlled maintenance phase of the trial. Volunteers were randomly divided into four groups:

• Assigned a GLP-1 drug + usual activity 

• Assigned a GLP-1 drug with supervised exercise

• A placebo + usual activity 

• A placebo with supervised exercise

Nearly all of the participants taking a GLP-1 medicine either maintained their lower weight, or shed even more, during the one-year supervised period. However, the drug + exercise group lost a bit more weight, including pounds from fat. 

The volunteers were then taken off the drug and the supervised exercise sessions stopped. After another year, 109 participants returned to the lab for analysis. Volunteers who had taken the GLP-1 drug alone had regained about two-thirds of the weight they had lost, and most of the regained weight was fat. The placebo groups had also regained weight. 

The group with the combination treatment of a weight loss drug plus exercise had the most success. While they did regain some of their prior weight, participants were still at least 10% lighter than they were at the beginning of the trial and had decreased fat mass and gained muscle. A possible explanation, researchers said, was that many participants had continued to exercise regularly on their own.

Craig Primack, MD, FACP, FAAP, FOMA, a physician specializing in obesity medicine and Senior Vice President of Weight Loss at Hims & Hers, says the study’s results make sense.

“Because these injectable medicines are so potent, people are not hungry. And when you're not hungry and you're not eating protein, you lose muscle,” Dr. Primack says. “If you stop taking the medicines and the hunger returns, you’ll gain all the weight back plus more.”

Muscle burns more calories than fat and contributes to a faster metabolism. Since weight loss is typically accompanied by decreased muscle mass, Dr. Primack says that means people would need to eat fewer calories to maintain their new lower weight.

This is why regular exercise is an important component during any weight loss journey—to counteract the loss of muscle.

“When you lose weight with these new medicines, you need an adequate amount of protein each day and you need exercise,” says Dr. Primack. “Strength training is better, but cardio is always good.”

To stay motivated, he recommends finding an activity you genuinely enjoy—whether that’s lifting weights, walking, practicing yoga or playing pickleball—because consistency is the most important factor. 

Working with a personal trainer or joining a sports team adds accountability and increases your odds of sticking with it. “Social is always better than solo,” he adds.

In the Danish study, researchers didn’t ask the GLP-1 + exercise group to continue working out on their own posttreatment. But Jessica Yu, Ph.D., a clinical psychologist and Senior Director of Patient Experience at Hims & Hers, says she’s not surprised that many of the volunteers maintained exercise routines.

“Physical activity tends to increase dopamine, so it can have a positive impact on mental and emotional health,” says Dr. Yu. She adds that since the study participants had already lost some weight, that may have provided more motivation to keep going. 

“Weight loss is a long game. It can take weeks or months to see differences, which can be demotivating,” explains Dr. Yu. “But when people can see that exercise is helping with their weight management, and helping their mood and other aspects of their lives, they’re more likely to do it.”

As Dr. Primack explains, there are four critical pieces for successful weight loss and long-term maintenance: anti-obesity medication, regular exercise, dietary changes that include an emphasis on protein, and behavioral modifications like learning how to eat healthier in social settings.

“The more pieces you put together, the more likely it is you’ll lose the weight and keep it off. It’s like the four legs of a chair,” he explains. “If you’re balancing on just one leg, that chair will fall over easily. But if you put all four legs on the ground, you have a much more stable base.” 

Dr. Primack adds, “As you lose weight, you start to feel good about yourself. As you're more active, you sleep better, which decreases your appetite. When your appetite goes down, you're not feeling sluggish from overeating, so you exercise some more. It's a positive feedback loop.”