New research indicates that popular weight-loss medications, specifically GLP-1 receptor agonists like semaglutide and tirzepatide, may lead to significant muscle loss, undermining the long-term health benefits associated with weight reduction. Conducted by the University of Virginia Health, the study highlights concerns that, while these drugs can effectively reduce waistlines, they do not improve fitness and could potentially harm muscle health.
Lead researcher Zhenqi Liu, MD, a Professor of Medicine and Diabetes at the UVA School of Medicine, 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 observation raises alarms about the implications of muscle loss, particularly axial muscle, which is crucial for maintaining posture and overall physical function.
The study emphasizes that while age-related muscle loss, known as sarcopenia, typically affects individuals at a rate of around 8% per decade, muscle loss resulting from these medications can account for between 25% and 40% of total weight lost. Such losses can increase the risk of cardiovascular disease, all-cause mortality, and a diminished quality of life.
Impact on Cardiorespiratory Fitness
Researchers aimed to explore the long-term consequences of muscle loss by reviewing data on the effects of GLP-1 receptor agonists on cardiorespiratory fitness (CRF). CRF, which refers to the body’s capacity to deliver oxygen to skeletal muscles during physical activity, is measured by maximal oxygen consumption, or VO2 max. Higher VO2 max values signify better cardiovascular fitness.
According to Siddhartha Angadi, PhD, an associate professor of kinesiology at UVA, “Cardiovascular fitness is a potent predictor of all-cause and cardiovascular mortality risk across a range of populations, including obesity, diabetes, and heart failure.” He highlighted findings from a recent study involving nearly 400,000 individuals globally, which concluded that CRF is far superior to weight status in predicting mortality risk.
The current study found that although GLP-1 drugs induce substantial weight loss, a considerable portion of this weight loss is derived from muscle mass. Importantly, the medications did not lead to improvements in VO2 max, raising concerns about their overall effectiveness in enhancing fitness levels.
Recommendations for Patients
Researchers advocate for further studies to better comprehend the effects of these medications on muscle and fitness. They point out that newer iterations of weight-loss drugs appear to have less drastic impacts on muscle mass, although they are still undergoing clinical trials.
For individuals currently taking or considering GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists, it is critical to consult healthcare providers regarding potential muscle loss. Dr. Liu advises, “This is an area of active research, and we are hopeful that better solutions are coming soon.” He emphasizes the importance of discussing strategies to preserve muscle mass with healthcare professionals.
The American Diabetes Association recommends screening for malnutrition and low muscle mass risk prior to initiating these medications. They also advocate for adequate protein intake and regular exercise throughout treatment.
Additional research is necessary to explore whether engaging in exercise while on GLP-1 medication influences cardiovascular fitness. Dr. Angadi noted, “Finally, exercise training during GLP-1 therapy remains to be assessed in its ability to preserve or improve VO2 max during GLP-1 therapy.”
The findings were published in The Journal of Clinical Endocrinology & Metabolism in March 2024, underscoring the need for an informed approach to weight-loss medication that prioritizes muscle health alongside weight management.