GLP-1 Weight Loss Drugs Linked to Reduced Activity and Muscle Loss

Adults using GLP-1 obesity medications like semaglutide may experience a decrease in physical activity and muscle loss, according to research presented at ENDO 2026. A study of 753 adults found daily steps dropped from 5,047 to 4,487, while experimental combinations with trevogrumab could reduce associated muscle loss by half.

Why does physical activity decrease during GLP-1 treatment?

Researchers analyzing 753 adults with obesity found that participants became less active after starting GLP-1 receptor agonists, which include semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). Data from activity-monitoring devices showed average daily steps fell from 5,047 to 4,487.

Time spent in moderate or vigorous physical activity also declined from 28 to 22 minutes per day. These reductions were most significant among men and individuals reporting muscle or joint pain.

Dr. Sajana Maharjan of HSHS St. John’s Hospital in the United States noted that the data contradicts the assumption that weight loss automatically makes exercise easier. “Although many assume that weight loss naturally leads to higher levels of physical activity, our data shows precisely the opposite,” Maharjan stated.

How can muscle loss be prevented?

While GLP-1 agonists effectively reduce body fat, they also cause a loss of lean mass. To address this, Regeneron laboratory researchers tested a combination of semaglutide and trevogrumab, a monoclonal antibody that blocks the muscle-limiting protein myostatin.

Some participants also received garetosmab, a drug targeting the protein activin A. Over 26 weeks of specialized body composition exams, researchers found that semaglutide alone was associated with higher muscle loss than the combination therapies.

Endocrinologist Alexander Benchimol reported that combining semaglutide with trevogrumab reduced the muscle loss typically seen with semaglutide by approximately half. This combination allowed participants to maintain lean mass while still achieving significant fat reduction.

What happens next for obesity therapies?

Trevogrumab and garetosmab remain in the research phase and are not yet approved for clinical use for this indication. Researchers noted that combining three different medications raised concerns regarding tolerability and adverse effects.

Future studies may focus on broader patient groups to evaluate these safety concerns. Specialists suggest that the next generation of obesity treatment may shift from simple weight reduction to a model that prioritizes muscle preservation and quality of life.

A sustainable long-term approach could likely involve a combination of medication, specific exercise programs, and muscle-protection strategies to ensure fat loss does not compromise overall health.

Frequently Asked Questions

Which medications were included in the physical activity study?
The study analyzed GLP-1 receptor agonists, specifically mentioning semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound).

How did the combination of semaglutide and trevogrumab affect the body?
According to Alexander Benchimol, this combination reduced muscle loss by about half compared to semaglutide alone, while still reducing body fat.

Are trevogrumab and garetosmab available for patients now?
No. These medications are currently in the research phase and are not approved for clinical use for this purpose.

Do you believe exercise programs should be mandatory requirements for patients prescribed weight-loss medications?