Mouse research suggests Ozempic may weaken muscles even when they don’t shrink, with most lean mass loss coming from organ size reduction. Credit: Shutterstock
Ozempic’s surge in popularity
for weight loss has sparked new concerns over its potential effects on muscle
mass and strength.
In mouse studies, the
drug reduced lean mass primarily by shrinking organs like the liver rather than
skeletal muscle. However, researchers found some muscles weakened even without
shrinking, raising questions about functional loss, especially in older adults.
Side Effects of
Ozempic and Lean Mass Loss
The widely used diabetes and weight-loss
medication Ozempic has seen a rapid rise in popularity, and with it, mounting
questions about its potential side effects. One concern is the reduction of
“lean mass” (body weight that is not fat), which has led to speculation that
the drug could be lowering muscle mass and strength.
A recent study in mice found that muscle
size did not decrease as much as expected, yet some muscles still became
weaker. This finding underscores the need for clinical trials to better
understand the drug’s full impact in people.
“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,” says Katsu Funai, PhD, associate professor of nutrition
and integrative physiology in the University of Utah College of Health and the
senior author on the study. “We have data in mice that suggest that things are
not as straightforward as they might seem.”
The results appear in Cell Metabolism.
Weight Loss Effects Beyond
Muscles
In the mouse study, Ozempic use led to a
roughly 10% drop in lean mass. Most of this loss came not from skeletal muscle,
but from other tissues such as the liver, which decreased in size by nearly
half. Researchers note that more work is needed to determine if these organ changes
also occur in humans and whether they carry any health risks.
“Loss of mass in metabolically active
organs, such as the liver, is expected as part of healthy weight loss,” says
Ran Hee Choi, PhD, research instructor in nutrition and integrative physiology
at U of U Health and co-first author on the study. In both mice and humans,
weight gain and loss can affect the size of organs like the liver without
affecting their function. “It’s unlikely that the observed lean mass loss
represents a serious adverse effect,” says Takuya Karasawa, PhD, postdoctoral
researcher in the U of U Molecular Medicine Program and co-first author on the
study.
Some skeletal muscles did shrink, on
average by about 6%, but this was not enough to account for the overall drop in
lean mass. Other muscles remained the same size.
The
researchers point out that some muscle reduction may simply be a return to
normal levels. When a person gains fat, their skeletal muscle often grows as
well because more muscle is needed to move the extra weight. Losing fat can
therefore also reduce muscle size without harming day-to-day physical function.
Muscle Strength
Decline Despite Size Maintenance
Interestingly, when the researchers tested
the amount of force the mice’s muscles could exert, they found that, for some
muscles, strength decreased as the mice lost weight, even when the size of the
muscle stayed roughly the same. For other muscles, strength was unchanged. It’s
unknown how weight loss drugs affect this balance in people, the researchers say.
A potential loss of strength when taking
Ozempic may be of particular concern for adults over the age of 60, who are at
higher baseline risk for muscle loss and reduced mobility. “The loss of
physical function is a strong predictor of not just quality of life but
longevity,” Funai adds.
Caution Against
Direct Human Extrapolation
The researchers caution against
extrapolating their results directly into humans, because mice and humans gain
and lose weight in different ways. In people, obesity is associated with lower
physical activity, but mice don’t tend to become less active when they gain
weight. And the mice in this study became overweight because they ate a
high-fat diet, whereas people become overweight for a wide variety of reasons
that include genetics, diet, sleeping patterns, and age.
Instead of drawing a one-to-one parallel
with humans, the researchers say their results emphasize the need for more
clinical studies. “There remains a significant need for validation in humans,
especially concerning muscle strength,” Karasawa says.
A Call for
Future Studies on Muscle Strength
Funai adds that clinical trials should
check for changes in muscle strength, not just for Ozempic, but also for future
weight-loss drugs. “There are many additional weight loss drugs that are in
clinical trials and coming out in the next three to five years,” Funai says.
“But with all those clinical trials, if they’re interested in measuring lean
mass loss, they need to consider physical function.”
“Our
findings are really interesting, but this is a preclinical model,” he adds. “We
need these data in people.”
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