With the increasing popularity of GLP-1 medications, researchers at WashU Medicine are investigating a crucial question: Does rapid weight loss lead to a decrease in muscle mass and strength?
A new clinical trial is exploring the effects of semaglutide medications like Wegovy on muscle mass and physical function following weight loss—and whether engaging in exercise can mitigate these effects.
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Previous research indicates that up to 40 percent of weight lost while using a GLP-1 medication may come from lean body mass, according to Dr. Samuel Klein, director of WashU Medicine’s Center for Human Nutrition. Approximately half of this loss is muscle.
Klein’s study particularly targets older women, who typically start with lower muscle mass compared to men or younger women.
“[Certain GLP-1 medications have been] approved by the FDA for individuals who are obese and those who are obese with Type 2 diabetes,” Klein explains. “Losing a significant percentage of muscle mass while being obese may enhance metabolic health, but it could also diminish physical function.”
The clinical trial aims to determine if a structured exercise regimen can help maintain muscle and enhance mobility during weight loss treatment.
Researchers will assess physical function through activities such as stair climbing, standing from a seated position, and six-minute walking tests.
All participants in the study will take semaglutide medication, but only one group will engage in supervised exercise training.
The research team anticipates that all participants will see some improvement in physical function simply from weight loss.
“Obese individuals generally have more muscle mass than those who are lean, and you require less muscle to move if you have less body weight,” Klein clarifies.
Nonetheless, researchers believe that exercise might offer additional advantages.
“We know that combining weight loss and exercise training in older adults who are frail enhances physical function more effectively than weight loss alone,” Klein states. “We anticipate that exercise training will help minimize the loss of lean body mass and muscle mass, leading to both muscle preservation and significant improvements in physical function.”
Klein hopes the study will alleviate concerns among healthcare providers and patients who are wary of semaglutide medications, demonstrating that pairing GLP-1 treatment with exercise therapy can result in patients being healthier and stronger overall.
The research team is currently looking for participants for the study: women aged 50 and over who are obese. During the one-year intervention, participants may earn up to $3,000 in compensation, alongside free GLP-1 medication, health assessments, and counseling. Those in the exercise group will also receive professional fitness training at WashU’s medical campus.
Participants are encouraged to complete a one-year follow-up program so researchers can monitor health changes post-medication.
The study commenced in October 2025 and is expected to run for three years, with preliminary findings potentially published by January 2028. Interested individuals can reach out to the Center for Human Nutrition at [email protected] or call 314-273-1879.
