Mice aren’t people, but they have a lot in common with humans genetically. And the furry rodents are often used in preliminary studies to help answer questions about where human research should go.
For University of Utah researchers, a recently completed mouse study published in the journal Cell Metabolism suggests the need to look more closely at whether the popular drug Ozempic and other semaglutide drugs could cause muscle weakness that needs to be addressed for those taking the medications to manage diabetes or lose weight.
The researchers hail the medications as a “significant breakthrough in pharmacological interventions to treat obesity.” But they note recent concerns that Ozempic and similar drugs cause “a loss of lean mass, potentially compromising physical function and quality of life, particularly in those susceptible to sarcopenia.”
Sarcopenia is the loss of muscle mass, strength and function associated with age. But there are also medical conditions that could lead to worries about weakened muscles, too, the study’s senior author, Katsu Funai, an associate professor of nutrition and integrative physiology at the University of Utah College of Health, told Deseret News.
The goal is not to downplay the importance of how Ozempic and related drugs can improve health by controlling blood sugar or causing weight loss, he added. But his team wants to point out that measures might be needed to protect against a potential negative side effect. If further study shows that a drug leads to weaker muscles — especially in a population that might be susceptible already to losing strength — then those folks might need tandem interventions that maintain or build muscle strength.
Funai said that besides age, recent surgeries, disabilities and other conditions might increase the risk of losing muscle strength. And quality of life is very much affected by muscle loss, which can lead to falls, injuries and inactivity, impacting overall health and well-being.
What the Ozempic study found
It’s generally assumed that loss of lean muscle leads to loss of muscle mass and weaker muscles. That may not be as straightforward as some believe. The university-led research found those losing weight with Ozempic also lost about 10% of lean mass, though not necessarily from skeletal muscles, but from tissue such as the liver, which shrank a lot.
“Loss of mass in metabolically active organs, such as the liver, is expected as part of healthy weight loss,” Ran Hee Choi, research instructor in nutrition and integrative physiology at University Health and co-first author on the study, said in a news release.
But both mice and humans can see organ size change alongside weight without a similar change in function. “It’s unlikely that the observed lean mass loss represents a serious adverse effect,” said Takuya Karasawa, postdoctoral researcher in the University of Utah Molecular Medicine Program and co-first author on the study.
But size of muscles and strength are very different things, Funai said. And loss of lean mass is not the same as muscle loss or its strength, either. The researchers found that even when a muscle stayed the same size, it in some cases lost strength, while in other muscles that didn’t happen.
What isn’t known — and needs to be studied, Funai said — is whether weight loss can lead to loss of muscle strength in some people and, if so, who would be impacted.
Funai emphasized again that their work in mice raises questions, but does not necessarily apply directly to humans. For one thing, as the study notes, rodents and people gain and lose weight differently. People with obesity are often less physically active, while having obesity doesn’t usually make mice more sedentary. And the mice were given obesity through a high-fat diet for the study, while people have many different reasons for weight gain, including genetics, diet, sleep patterns and age.
Funai said it is very common for people to not realize they have lost strength in their muscles, but when it’s tested, the loss is clear.
“When they’re opening a jar or when they have to do flights of stairs that they don’t usually do or have to carry something, then they might notice. It’s something that they may not be aware of” otherwise, he said.
He added that the loss of muscle mass and loss of muscle strength were dose dependent and time dependent, meaning that how long and how much Ozempic was given mattered. And the dose that was higher and where loss was more sustained was higher than would be given to people.
It was noteworthy that loss of muscle mass and loss of force or strength weren’t always coupled and that fact was not uncommon.
The study points out the need for clinical trials that directly look at whether muscle strength is lost and if so, in which populations, Funai said. And those studies should consider not just Ozempic and other semaglutide weight-loss drugs, but those in development, he added.
While studies frequently consider lean mass loss, physical function is an important issue that may not be so straightforward, he said. But it’s critically important for those who may be vulnerable to losing strength and gaining associated risks.
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