New research suggests popular weight loss drugs like Ozempic and Wegovy may affect more than just fat, raising questions about muscle strength and organ size after significant weight loss.
University of Utah scientists studied semaglutide, the active ingredient in weight loss medications, in mice.
In the study, published in the journal Cell Metabolism, researchers revealed “unexpected effects,” highlighting that lean mass, or body weight that isn’t fat, dropped about 10 percent. Most of the loss came from non-muscle tissues, particularly the liver, which shrank by nearly half. Some skeletal muscles lost around 6 percent of their size, while others remained unchanged.
Despite relatively small changes in muscle size, certain muscles became weaker. Researchers said this could be especially concerning for adults over 60, who already face higher risks of muscle loss and reduced mobility.
“The loss of physical function is a strong predictor of not just quality of life but longevity,” said Katsu Funai, the senior author on the study.
The findings challenge the assumption that lean mass loss comes mainly from skeletal muscle. Instead, they point to changes in metabolically active organs, such as the liver, which can shrink during healthy weight loss without harming function.
“It’s unlikely that the observed lean mass loss represents a serious adverse effect,” said Takuya Karasawa, co-first author on the study.
Still, scientists emphasize that further human studies are necessary to determine whether similar effects occur in humans and whether they pose health risks.
“There remains a significant need for validation in humans, especially concerning muscle strength,” Karasawa said.
They also suggest that future clinical trials should track not only lean mass but also muscle strength and physical function, especially as more weight loss drugs enter the market.
“There are many additional weight loss drugs that are in clinical trials and coming out in the next three to five years,” Funai said. “But with all those clinical trials, if they’re interested in measuring lean mass loss, they need to consider physical function.”
