Ozempic Could Impact Strength, Not Just Muscle Size
Ozempic may weaken muscle strength in mice even without major loss of muscle mass.
Ozempic® (semaglutide) has transformed diabetes and weight-loss treatment, yet questions about its impact on muscle remain.
A team at the University of Utah investigated the issue in mice, finding that while muscle mass changes were modest, muscle strength dropped sharply in some cases.
“We have data in mice that suggest that things are not as straightforward as they might seem,” said senior author Dr. Katsu Funai, an associate professor of nutrition and integrative physiology and adjunct associate professor of biochemistry at the University of Utah Health.
Ozempic and lean mass loss
Ozempic is a drug that mimics a natural hormone to lower blood sugar and curb appetite. It’s widely used to treat type 2 diabetes and to help people lose weight. Clinical trials, such as the STEP 1 study, show users shed ~15% of their body weight over 68 weeks. However, ~45% of that weight loss came from lean mass rather than fat, raising alarms about what exactly is being lost.
Losing lean tissue during weight loss isn’t unusual, and typically, a quarter of the lost weight often comes from lean mass. However, the STEP 1 results showed a much higher proportion lost.
Since muscle strength underpins mobility and long-term health, these results raised the concern that these drugs might be trading fat loss for muscle weakness.
“For individuals who may be losing muscle mass, we need to know that they’re actually losing muscle mass,” said Funai.
To tackle this, the new study used obese mice treated with semaglutide. Funai and colleagues investigated how muscle size and muscle strength change separately.
Ozempic changed muscle size and strength in mice
Male mice were first made obese by eating a high-fat diet for 12 weeks. They were then split into groups and given daily injections of either a standard “clinical” dose of semaglutide (3 nmol/kg) or a much higher dose (30 nmol/kg). Treatment lasted either one or three weeks. The team tracked changes in fat and lean mass, measured organ sizes and tested muscle strength by stimulating isolated leg muscles outside the body.
The mice dropped 19–26% of their body weight, mostly from fat, which fell by 43–52%. Lean mass also declined by ~9–14%. Closer analysis showed that most of this loss wasn’t muscle – it came from metabolically active organs. The liver, for example, shrank by nearly 50%.
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Nearly all the lean mass loss in mice occurred during the first week of semaglutide treatment, while fat mass continued to fall steadily throughout the three weeks.
Some muscles shrank modestly (~6%), while others stayed the same. These reductions didn’t push muscles below the levels seen in lean control mice. In other words, the muscle mass lost was mostly a reversal of the extra tissue gained during obesity.
When looking at muscle strength, the fast-twitch extensor digitorum longus muscle lost ~20% of its force after just 1 week, even when its size hadn’t changed much. This weakness was temporary at the clinical dose but sustained at the higher dose. The slow-twitch soleus muscle stayed stable.
Extensor digitorum longus
A fast-twitch leg muscle in the front of the lower leg that helps extend the toes. It’s commonly studied because it responds quickly but tires easily.
Soleus muscle
A slow-twitch calf muscle used for standing and walking. It is built for endurance and resists fatigue.
This mismatch between size and strength echoes patterns seen in aging and cancer cachexia.
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“The loss of physical function is a strong predictor of not just quality of life, but longevity,” said Funai.
What Ozempic’s effects on muscle could mean for people
The findings suggest that Ozempic can weaken muscles without large changes in muscle size – raising questions about how the drug may affect people, especially older adults who are already at higher risk of muscle loss and reduced mobility. If strength can decline while muscle mass stays the same, then physical function may be as important as body composition when weighing drug safety.
At the same time, the authors stress that the lean mass loss seen here isn’t automatically harmful. “It’s unlikely that the observed lean mass loss represents a serious adverse effect,” said first author Dr. Takuya Karasawa, a postdoctoral researcher in the University of Utah Molecular Medicine Program.
Some of the changes were expected, such as shrinking of the liver, which happens naturally with weight loss and doesn’t necessarily impair function.
The study has its limits. It was short, just one to three weeks, and it was done in mice, which gain and lose weight differently from people. Mice stay active even when obese, unlike many people who reduce their activity.
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“Our findings are really interesting, but this is a preclinical model,” Funai adds. “We need these data in people.”
Future clinical trials should measure not only lean mass but also muscle strength.
“There are many additional weight loss drugs that are in clinical trials and coming out in the next three to five years,” said Funai. “But with all those clinical trials, if they’re interested in measuring lean mass loss, they need to consider physical function.”
Reference: Karasawa T, Choi RH, Meza CA, et al. Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice. Cell Metab. 2025;37(8):1619–1620. doi: 10.1016/j.cmet.2025.07.004
This article is a rework of a press release issued by the University of Utah Health. Material has been edited for length and content.
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