Warning of unexpected effects of ozempic on muscle function

As use of Ozempic , the popular anti-diabetic and weight-loss drug, skyrockets, so do concerns about its side effects. One of these is the loss of lean body mass (non-fat body weight), raising concerns that Ozempic may be reducing muscle mass and strength.

Now, research in mice suggests that administering semaglutide—the molecule marketed under the name Ozempic or Wegovy—doesn't reduce muscle mass as much as expected, but it does affect muscle function.

Published in the journal Cell Metabolism , the study shows that in some muscle types, the ability to generate force was observed to decline by around 20%, disproportionately greater than the loss of muscle mass.

These data suggest an urgent need for clinical studies to determine the full effects of popular medications.

"If we really want to help people who might be losing muscle mass, we need to know that they're actually losing it," says Katsu Funai, a professor at the University of Utah School of Public Health and senior author of the study.

Researchers found that Ozempic-induced weight loss reduced lean mass by approximately 10%. Most of this weight loss came not from skeletal muscle, but from other tissues such as the liver, which was reduced by almost half.

However, researchers acknowledge that more research is needed to determine whether similar changes in organ size occur in humans and whether these changes pose any risks.

According to the study's authors, loss of mass in organs such as the liver can occur during healthy weight loss without affecting its function, so it is not considered a serious adverse effect.

Part of this muscle loss is due to a return to normal, they say. Increased fat also often leads to an increase in skeletal muscle , as the body must work harder to move. Therefore, fat loss can lead to muscle loss without affecting overall quality of life.

Interestingly, when the researchers tested the force the mice's muscles could exert, they found that in some muscles, strength decreased as the mice lost weight, even when muscle size remained virtually the same. In other muscles, strength remained unchanged.

However, how weight-loss drugs affect this balance in people is unknown, researchers say.

A potential loss of strength while taking Ozempic may be especially concerning for people over 60, who are at higher risk of muscle loss and reduced mobility. "Loss of physical function is a strong predictor not only of quality of life, but also of longevity," Funai adds.

The researchers caution against directly extrapolating their results to humans, as mice and humans gain and lose weight differently.

In humans, obesity is associated with decreased physical activity , but mice do not tend to become less active as they gain weight. Furthermore, the mice in this study became overweight due to a high-fat diet, whereas humans become overweight for a variety of reasons, including genetics, diet, sleep patterns, and age.

Rather than drawing a direct parallel with humans, they say their results emphasize the need for further clinical studies. "There remains a significant need for human validation, especially with regard to muscle strength," Karasawa says.

Joana Nicolau, from the Balearic Islands Health Research Institute (IdISBa), shares a similar opinion. She told the Science Media Centre that the results reinforce the message that weight loss must be approached holistically. Nicolau asserts that semaglutide, effective in weight loss and improving complications associated with obesity and cardiovascular risk, should be combined with a protein-adequate diet and strength training to preserve muscle mass and optimize metabolic benefits. " Unsupervised use can compromise long-term results ."

Future clinical trials, the study authors write, should evaluate changes in muscle strength, not only with Ozempic, but also with future medications.