A team of researchers from the University of Copenhagen has revealed that exercise in combination with weight loss medication can help sustain a healthy weight.

Exercise is the key to maintaining the effects of weight loss medication.

This was the main finding in a study led by Signe Torekov, Professor at the University of Copenhagen. The study was the first to investigate weight maintenance and exercise in connection with obesity drugs using glucagon-like peptide 1 (GLP-1) receptor agonists.

The results were published in the article Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial in eClinicalMedicine published by The Lancet.

We talked with first author Simon Kjær Jensen, PhD, postdoc, and third author, DDEA grant recipient Rasmus Michael Sandsdal, MD, PhD student, about the study.

Finding the Winning Combo

New weight loss medications like Wegovy, Ozempic, and Saxenda uphold their high popularity. All of them are glucagon-like peptide-1 (GLP-1) receptor agonists, which were initially developed as a treatment for type 2 diabetes. GLP-1 receptor agonists trigger the GLP-1 receptor, inhibit appetite, and slow gastric emptying, resulting in an effective obesity treatment.

“One of the biggest challenges with weight loss is maintaining it. Even as effective as these new treatments are, we still see a lot of people regaining weight after stopping the treatment,” says Simon Kjær Jensen. “Furthermore, we know up to half of the people discontinue treatment within the first year of prescription. So, we wanted to investigate the most sustainable method of maintaining weight loss after stopping active weight loss treatment.”

Simon and his colleague’s study involved 109 adults with obesity who underwent an eight-week low-calorie diet resulting in a weight loss of 13.1 kg. Participants in the trial were then divided into four groups for one year of weight loss maintenance. The groups received either supervised exercise, a once-daily GLP-1 receptor agonist, a combination of exercise and GLP-1 receptor agonist, or a placebo. The study was conducted in collaboration with Hvidovre Hospital, Department of Endocrinology, and the Department of Biomedical Sciences, University of Copenhagen.

The study found that the people who exercised while using a weight loss drug kept off more weight after stopping the medication than those who did not exercise.

A Need for New Maintenance and Exit Plans

The Danish study indicates that it is possible to preserve a healthy weight even after quitting weight loss medication, but it requires that a structured exercise program is co-administered with weight loss medication.

Rasmus Michael Sandsdal says: “Our results indicate that GLP-1 treatments can be effective in facilitating simultaneous changes in habits and behaviour, opening a sort of therapeutic window in which sustainable behavioural changes can be introduced.”

Simon adds that “significantly reducing body weight might lower barriers to engaging in physical activity, such as knee problems. However, physical activity does not increase automatically with weight loss. It requires a structured and supervised plan.”

As the two authors of the study explain, the means to sustaining a healthy weight can differ from person to person and might require more personalised strategies. In their study, participants were supervised in following their exercise plans, which is one way of helping people keep off the weight.

“After the treatment has ended, it will not be enough to tell patients to eat healthy and be active – it requires more professional insight and perhaps more personal insights into the patient’s situation. Finding a way to translate our results to action requires interdisciplinary approaches,” says Rasmus Michael Sandsdal.

Media Attention and Future Focus

Simon, Rasmus, and their colleague’s study has gained attention both nationally and internationally, with articles in the Danish news outlet TV2 Nyhederne and The Washington Post, among many others.

”It’s a timely and important subject, so it was nice to see it gain media traction,” says Simon. “It’s vital that this knowledge is shared both with people living with obesity and with those who treat it.”

There are still many other aspects to investigate regarding metabolism, weight loss, and weight loss treatment, and both Rasmus and Simon continue their work in this field.

“Some of the things we’re looking at in one of our current projects are how GLP-1-based treatments work in the brain in terms of which systems they engage and how much of the action is conscious or unconscious,” says Rasmus. “The DDEA has supported me in these current investigations in a study collaboration with Signe Torekov (including postdoc Sarah Byberg), Jens-Christian Holm, Torben Hansen, and Gitte Moss Knudsen.”

“It’s important to add that mental health is also a big factor, as well as demographic and social circumstances, so those are other aspects that we wish to factor in for the future,” Rasmus concludes.

Contact

Simon Kjær Jensen
PhD, Postdoc,
Clinical Translation Metabolism Group – Torekov Group
Department of Biomedical Sciences
University of Copenhagen
simon.jensen@sund.ku.dk

Rasmus Michael Sandsdal
MD, PhD Fellow
Clinical Translation Metabolism Group – Torekov Group
Department of Biomedical Sciences
University of Copenhagen
rasmus.sandsdal@sund.ku.dk

Publication

Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial

Simon Birk Kjær Jensen, Martin Bæk Blond, Rasmus Michael Sandsdal, Lisa Møller Olsen, Christian Rimer Juhl, Julie Rehné Lundgren, Charlotte Janus, Bente Merete Stallknecht, Jens Juul Holst, Sten Madsbad, Signe Sørensen Torekov

eClinicalMedicine (February 2024)

DOI: https://doi.org/10.1016/j.eclinm.2024.102475