A new study raises important questions about the long-term health effects of GLP-1 medications, such as Ozempic and Wegovy. While these drugs are highly effective for weight loss, researchers at the University of Virginia say they may also lead to a significant loss of muscle mass, without delivering improvements in cardiorespiratory fitness.
“Some patients literally told me that they felt that they were losing muscle or muscle was slipping away from them while they were on these medications,” said Dr. Zhenqi Liu, professor of medicine and former chief of UVA Health’s Division of Endocrinology and Metabolism. “This is a serious concern.”
In a new review published in the Journal of Clinical Endocrinology & Metabolism, the team found that GLP-1 drugs help people lose both fat and fat-free mass, including muscle, which can account for 25-40% of total weight loss. That’s far more than the typical 8% loss of fat-free mass that happens naturally with aging over a decade.
The researchers focused on how this shift affects cardiorespiratory fitness, or VO₂max, which measures how efficiently the body uses oxygen during exercise. VO₂max is widely recognized as a predictor of overall health and risk of death, particularly for people with obesity, type 2 diabetes or heart failure.
While GLP-1 drugs improved some markers of heart function, they didn’t lead to measurable improvements in VO₂max.
“Once CRF [cardiorespiratory fitness] was factored in, body weight failed to predict the risk of mortality,” said coauthor Dr. Siddhartha Angadi, a cardiovascular exercise physiologist. “This is why it’s so important to understand the effects of this new class of drugs on it.”
In other words: losing weight doesn’t always mean gaining health, especially if you’re losing muscle along the way.
The study’s authors say that pairing GLP-1 drugs with exercise and proper nutrition may help preserve muscle and protect long-term health. The American Diabetes Association currently recommends screening patients for low muscle mass and promoting adequate protein intake and regular exercise when using these medications.
“Exercise training during GLP-1 therapy remains to be assessed in its ability to preserve or improve VO₂max,” Angadi said.
The researchers emphasized the need for more studies and are hopeful that future medications, such as monoclonal antibodies now in development, may help offset lean-muscle loss. But in the meantime, they urge patients to have honest conversations with their health care providers about how to protect muscle mass and monitor cardiorespiratory fitness during GLP-1 treatment.
The research was funded by the National Institutes of Health.