Exercise remains essential alongside GLP-1 obesity treatments

As GLP-1 receptor agonists reshape obesity treatment, a new medical perspective published in the Journal of the American Medical Association, or JAMA, underscores a persistent gap in care: integrating exercise into weight management in ways patients can sustain.

The perspective, "The Conundrum of Exercise for Weight Management in the GLP-1 Receptor Agonist Era," examines the evolving role of physical activity alongside medications such as semaglutide, liraglutide and other GLP-1-based therapies. Authors included Pennington Biomedical's Steven B. Heymsfield, M.D., and Harvard University's Daniel E. Lieberman, Ph.D., and Daniel H. Aslan, Ph.D.

GLP-1 therapies have been shown to reduce caloric intake by up to 39% and produce substantial weight loss. By comparison, standard physical activity recommendations (150 minutes per week) yield relatively modest calorie expenditure.

The authors emphasize that exercise's value extends far beyond energy balance – it has important complementary effects, including improved insulin sensitivity, increased fat oxidation and, perhaps most importantly, preservation of fat-free mass. Exercise plays a critical role in preserving muscle mass – an area of concern with GLP-1 therapies. Studies show that a large percentage of weight loss on GLP-1 medications may come from fat-free mass, including muscle, increasing the risk of sarcopenia.

The perspective also highlights a key clinical concern: Up to 60% of patients discontinue GLP-1 medications within a year, with many regaining a significant portion of lost weight. Regular physical activity, particularly at higher volumes, plays an important role in mitigating this regain.

Despite its proven benefits, exercise remains difficult for many patients to sustain. Barriers include time constraints, physical limitations, lack of access to facilities and that, for some, exercise can feel difficult and unrewarding.

To improve outcomes, the authors encourage clinicians to move beyond general advice and instead develop individualized, practical strategies. These include assessing activity levels, addressing patient-specific barriers, emphasizing health benefits beyond weight loss and helping patients identify enjoyable, sustainable forms of movement.

The perspective concludes that GLP-1 therapies should complement – not replace – exercise, and that improving adherence is now the central challenge in translating exercise's proven benefits into real-world impact.

"Although GLP-1 receptor agonists offer powerful new opportunities for losing weight, they do not diminish the manifold benefits of exercise and instead highlight the need to translate exercise's efficacy into effectiveness," the authors concluded.