As GLP-1 medications continue to grow in popularity, researchers at WashU Medicine are studying an important question: Does rapid weight loss come at the expense of muscle and strength?
A new clinical trial is examining how semaglutide medications such as Wegovy affect muscle mass and physical function after weight loss—and whether exercise can help offset those effects.
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Previous studies have shown that as much as 40 percent of weight lost while taking a GLP-1 medication can come from lean body mass, says Dr. Samuel Klein, director of WashU Medicine’s Center for Human Nutrition. About half of that loss is muscle.
Klein’s study focuses specifically on older women, who often begin with lower muscle mass than men or younger women.
“[Certain GLP-1 medications have been] approved by the FDA for people who are obese and people who are obese with Type 2 diabetes,” Klein says. “If you lose a high percentage of your muscle mass and you’re obese, you may improve your metabolic health, but you could make your physical function go down.”
The clinical trial is designed to test whether a structured exercise program can help preserve muscle and improve mobility during weight loss treatment.
Researchers are measuring physical function through tasks such as stair climbing, standing from a seated position, and six-minute walking tests.
Every participant in the study takes semaglutide medication, but only one group participates in supervised exercise training.
The research team expects all participants to experience some improvement in physical function simply from losing weight.
“People who are obese generally have more muscle mass than people who are lean, and you need less muscle to move around if you have less body weight to carry,” Klein explains.
Still, researchers believe exercise may provide additional benefits.
“We know that weight loss and exercise training in older adults who are frail improves physical function better than weight loss alone,” Klein says. “We think exercise training will reduce the loss of lean body mass and muscle mass as well, so you’ll have both preservation of muscle and a significant improvement in physical function.”
Klein hopes the study will help address concerns among physicians and patients who are skeptical of semaglutide medications, showing that combining GLP-1 treatment with exercise therapy could leave patients healthier and stronger overall.
The research team is currently seeking participants for the study: women age 50 and older who are obese. During the one-year intervention period, participants may receive up to $3,000 in compensation, along with free GLP-1 medication, health assessments, and counseling. Those assigned to the exercise group also receive professional fitness training at WashU’s medical campus.
Participants are encouraged to complete a one-year follow-up program so researchers can observe health changes after stopping the medication.
The study began in October 2025 and is expected to continue for three years, with early findings potentially published as soon as January 2028. Those interested in participating can contact the Center for Human Nutrition at [email protected] or 314-273-1879.
