Weight-loss medications such as semaglutide and tirzepatide have gained popularity for their effectiveness in reducing body weight. However, recent findings from researchers at University of Virginia Health indicate that these GLP-1 receptor agonists (GLP-1RAs) may not enhance overall fitness and could lead to significant muscle loss. This muscle loss raises concerns about the long-term health benefits typically associated with weight reduction.
The study, led by Zhenqi Liu, MD, a Professor of Medicine and Diabetes at UVA School of Medicine, highlights a critical side effect of these medications: while users may experience rapid weight loss, it is often accompanied by a considerable loss of fat-free mass, primarily muscle. Dr. Liu noted, “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.” This muscle loss poses serious risks, including increased chances of cardiovascular disease and decreased quality of life.
According to the research, regular aging can result in a muscle loss of about 8% per decade. In contrast, individuals taking GLP-1RAs may experience 25% to 40% of their total weight loss coming from muscle loss. This discrepancy raises significant concerns about the overall health implications of these weight-loss drugs.
Impacts on Cardiorespiratory Fitness
The research team sought to understand the implications of muscle loss on cardiorespiratory fitness (CRF), which is the body’s ability to deliver oxygen to muscles during physical activity. The gold standard measure of CRF is maximal oxygen consumption, or VO2 max. Higher VO2 max values indicate better fitness levels and efficiency in utilizing oxygen during exercise.
Dr. Siddhartha Angadi, an associate professor of kinesiology at UVA, emphasized the importance of CRF, stating, “Cardiovascular fitness is a potent predictor of all-cause and cardiovascular mortality risk across a range of populations.” His team’s previous research, which analyzed mortality outcomes for nearly 400,000 individuals globally, concluded that CRF was a more reliable predictor of mortality than body weight. Once CRF was taken into account, body weight alone failed to indicate mortality risk.
In their findings, the researchers observed that while GLP-1 drugs resulted in significant weight loss, much of this reduction was attributed to muscle rather than fat. Furthermore, these medications did not demonstrate any improvement in VO2 max, which is concerning for those relying on these drugs for weight management.
Researchers have called for additional studies to further explore the relationship between these medications, muscle health, and cardiovascular fitness. Newer formulations of injectable weight-loss drugs may not have the same detrimental effects on muscle mass, but they are still undergoing clinical trials.
Recommendations for Patients
Individuals currently taking or considering GLP-1RAs or dual GLP-1/GIP receptor agonists are encouraged to consult healthcare professionals about the potential for muscle loss. Dr. Liu emphasized, “This is an area of active research, and we are hopeful that better solutions are coming soon.” He noted the importance of discussing strategies to preserve muscle mass with healthcare providers.
The American Diabetes Association recommends screening for malnutrition and low muscle mass risk before starting these medications. They also advocate for adequate protein intake and regular exercise during treatment to mitigate muscle loss.
Finally, further investigation is needed to determine whether exercise while on GLP-1 medications can positively influence cardiovascular fitness. Dr. Angadi pointed out that “exercise training during GLP-1 therapy remains to be assessed in its ability to preserve or improve VO2 max.”
The comprehensive study was published in The Journal of Clinical Endocrinology & Metabolism, reinforcing the need for ongoing research into the effects of GLP-1 medications on muscle health and overall fitness.
