Ozempic Reduces 'Non-Mass' Body Weight Through Organs, Not Muscles

A new study by researchers at the University of Utah, published in Cell Metabolism, sheds light on a long-standing concern: whether the popular obesity drug Ozempic (semaglutide) actually “burns” muscle rather than fat. In a mouse model, the researchers showed that while overall lean mass did drop by nearly 10 percent after taking Ozempic, much of that decline was not in skeletal muscle but in metabolically active organs, primarily the liver.

Key findings of the study

• Lean mass – 10% when losing weight. Mice on a high-fat diet given semaglutide lost an average of 20% of their total weight, of which about 10% was lean tissue.
• The liver "shrank" by almost half. Histological analysis showed that the volume and mass of the liver in recipient mice decreased by 40-50%, while muscle mass fell by only 6% in the most susceptible muscle groups, and remained virtually unchanged in others.
• Muscles are smaller—but not always weaker. In strength tests, some muscles showed a decrease in force capacity (by 8–12%) even though their volume had changed only slightly, while others retained both volume and strength.

Why Blood Won't Turn Into Collagen

“We expected that the loss of lean mass from Ozempic would be mostly from muscle rather than organs,” says Katsu Funai, the senior author of the paper. “But our analysis showed that the liver and other metabolic tissues, such as the lungs and kidneys, were the major contributors to this effect.” He says that the reduction in liver volume during weight loss is “a sign of healthy metabolism,” rather than a dangerous side effect.

Muscle strength vs muscle size

Ran Hee Choi, a co-author of the study, points out that the 6% reduction in skeletal muscle volume may partly reflect a “return” to the baseline, unaccumulated level during obesity: more fat mass leads to muscle hypertrophy due to the body’s need to carry and support this extra weight. But the critical question remains: do the mice actually lose their physical strength as a result of taking semaglutide? “We saw a decrease in strength in some muscle groups even without a significant loss in their volume,” says Takuya Karasawa.

Why is this important for people over 60?

Loss of muscle strength (dynapenia), rather than mass itself, is considered one of the main predictors of poor quality of life and even mortality in older people. “If Ozempic reduces strength in mice, we urgently need to test it in humans, especially those over 60 who are already predisposed to sarcopenia,” Funai warns.

Clinical trials are needed

The authors stress that the mouse findings cannot be directly transferred to humans: mice do not become sedentary when obese in the same way as humans, and obesity in their model is induced solely by diet. Instead, they call for targeted clinical trials where:

1. Not only will the change in lean mass in patients on semaglutide be measured, but also the strength of specific muscle groups.
2. They will track which organs are shrinking the most: the liver, kidneys, heart?
3. They will compare this data with functional tests: walking speed, climbing stairs, and grasping a weight.

“We are on the cusp of dozens of new weight-loss drugs,” Funai says. “If they can also affect muscle and strength, clinical trials should immediately include physical function tests, rather than relying solely on DXA and lean mass measurements.”

This study opens the prospect of a deeper understanding of how semaglutide-based drugs affect human tissues and highlights the need for comprehensive patient monitoring—from organ size to muscle strength—for the safety and effectiveness of obesity therapy.