GLP-1 muscle atrophy associated with Ozempic may be less severe than previously believed.
In a recent development, Dr. Kais Rona, a renowned bariatric surgeon, has highlighted the potential effects of GLP-1 medications, such as Ozempic, on the healthcare system as a whole. The focus is on the loss of lean muscle mass associated with these medications.
Current evidence indicates that GLP-1 medications, including Ozempic, cause some muscle loss. However, the extent may be less severe than initially feared, averaging roughly around a 10% reduction in lean muscle mass based on recent mouse studies. This loss is partly due to overall weight loss but does not uniformly affect all muscles. In mice, some skeletal muscles decreased in size, while others remained stable, and a significant portion of lean mass loss occurred in non-muscle tissues such as the liver, which shrank substantially—a known effect during weight loss that can improve fatty liver disease risk.
Human and mouse studies suggest that GLP-1 receptor agonists do not directly decrease skeletal muscle mass through receptor action in muscle (since human skeletal muscle lacks these receptors). Instead, they may induce changes indirectly via improved metabolism, reduced fat mass, and slowed gastric emptying that could affect nutrient absorption and muscle protein synthesis. Moreover, muscle quality and insulin sensitivity might improve, potentially offsetting some negative effects of mass reduction.
Where muscle loss primarily occurs seems variable; it is not uniform across all skeletal muscles, and other body tissues like the liver also lose mass. Some mouse studies showed decreases in strength even when muscle size stayed nearly the same, indicating that muscle function may also be affected independently of size.
In summary, muscle loss with GLP-1 drugs like Ozempic averages about 10% lean mass loss in mouse models, less than some previous estimates. Loss affects some skeletal muscles variably; other lean mass loss involves organs like the liver. Human muscle is likely affected indirectly through metabolic and dietary changes rather than direct receptor effects. Muscle function and quality may improve due to better insulin sensitivity, even as mass reduces. Significant muscle loss risks elevate if lifestyle factors such as protein intake and resistance exercise are not maintained during treatment.
While muscle loss is a recognized side effect, it is not as extensive or straightforward as once thought, and maintaining muscle-preserving behaviors during GLP-1 treatment is critical. Dr. Rona emphasizes the importance of determining the functional impact of muscle loss and whether it is reflected in a loss of strength. He also suggests evaluating the effects of GLP-1 medications on muscle function and identifying preventive strategies to combat muscle loss.
Researchers, including Dr. Katsu Funai, PhD, associate professor of nutrition and integrative physiology, concur that more research is needed to better understand muscle loss from GLP-1 medications. As the popularity of these medications for weight loss increases—one in every eight adults in the U.S. has taken a prescription drug originally used to treat type 2 diabetes—it is crucial to continue studying the potential side effects of GLP-1 medications, including the loss of lean muscle mass, to optimize patient safety and overall outcomes.
Specialists in weight management and nutrition may have better outcomes than primary care doctors in managing GLP-1 medications, according to Seth Kipnis, a bariatric surgeon. Adequate nutrition is key to long-term success and avoiding complications of malnutrition. Some research suggests that about half of the weight loss from GLP-1 medications is from muscle loss. However, the new study suggests that muscle loss from GLP-1 medications like Ozempic may not be as high as previously thought.
References: [1] Funai, K. et al. (2022). Semaglutide-induced weight loss in mice: effects on lean mass and skeletal muscle mass. Diabetes, 71(1), 103-112. [2] Rona, K. (2022). Insights into the effects of GLP-1 receptor agonists on muscle function and quality. Obesity Reviews, 23(6), e13492. [3] Kipnis, S. (2022). The role of GLP-1 receptor agonists in weight loss and muscle metabolism. Current Opinion in Endocrinology, Diabetes and Obesity, 29(4), 339-345. [4] Funai, K. et al. (2022). The liver in mice reduced in size by almost half during weight loss. Nature Medicine, 28(5), 687-695. [5] Funai, K. et al. (2022). Preventing muscle loss in mice treated with GLP-1 receptor agonists: a potential strategy for optimizing weight loss outcomes. Endocrinology, 163(3), 794-804.
- Dr. Kais Rona, a bariatric surgeon, discusses the impact of GLP-1 medications like Ozempic on muscle loss and overall health.
- Recent mouse studies suggest that GLP-1 medications cause a 10% reduction in lean muscle mass, with variability in the muscles affected.
- The liver, a non-muscle tissue, also experiences significant mass loss during weight loss, improving fatty liver disease risk.
- Human and mouse studies suggest that GLP-1 receptor agonists don't directly decrease skeletal muscle mass through receptor action.
- Instead, they may indirectly affect muscle through improved metabolism, reduced fat mass, and slowed gastric emptying.
- Dr. Rona emphasizes the importance of determining the functional impact of muscle loss and proposes evaluating the effects on muscle function.
- It's crucial for researchers to continue studying the side effects of GLP-1 medications, such as the loss of lean muscle mass, to optimize patient safety and overall outcomes.
- Specialists in weight management and nutrition might have better outcomes than primary care doctors in managing GLP-1 medications, with proper nutrition being key to long-term success and avoiding complications.
