Ozempic and other semaglutide-based medications are helping millions lose weight. But as their popularity grows, so do questions about how these drugs affect more than just the number on the scale.
One concern? Muscle health.
A new study from University of Utah Health, published in Cell Metabolism, suggests that semaglutide may affect strength in ways not fully captured by measuring weight or muscle size alone.
Researchers treated mice with semaglutide and observed what happened as the animals lost weight. Lean mass declined by about 10%, but surprisingly little of that loss came from skeletal muscle. Instead, much of it came from metabolically active organs, most notably the liver, which shrank by nearly half.
“Loss of mass in metabolically active organs, such as the liver, is expected as part of healthy weight loss,” said Ran Hee Choi, PhD, co-first author of the study.
Still, the degree of change observed in the liver was striking.
Other organs likely changed in size too, though this study focused on the liver and muscle. In terms of muscle mass, some skeletal muscles shrank by about 6%. Others didn’t shrink at all.
That sounds reassuring until you look at strength. When researchers tested how much force the mice’s muscles could produce, some were weaker than expected. In fact, even muscles that had stayed the same size had lost strength.
“We have data in mice that suggest that things are not as straightforward as they might seem,” said senior author Katsu Funai, PhD. “If we want to really help the individuals who may be losing muscle mass, then we need to know that they're actually losing muscle mass.”
In other words, it’s not just about how big a muscle is; it’s about what it can do. That distinction could be especially important for adults over 60, who are already at higher risk for muscle loss and decreased mobility.
“The loss of physical function is a strong predictor of not just quality of life but longevity,” Funai said.
The researchers cautioned that these results are from mice, not humans. Mice and people gain and lose weight differently, and human obesity has a broader range of contributing factors, including sleep, genetics, age and physical activity.
Still, the findings raise an important point: clinical trials for weight-loss drugs may need to go beyond measuring weight and lean mass. According to the researchers, muscle function, especially strength, should be part of the equation.
“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.”
And while this study opens the door for new questions, the team agrees on one thing: answers will need to come from human trials.
“Our findings are really interesting, but this is a preclinical model,” Funai said. “We need these data in people.”
This research was supported by the U.S. National Institutes of Health and the Japan Society for the Promotion of Science.