As the popularity of weight-loss medications surges, concerns are mounting over their potential adverse effects on muscle health. Recent studies indicate that rapid weight loss facilitated by glucagon-like peptide-1 (GLP-1) receptor agonists—commonly prescribed drugs like semaglutide (Ozempic) and liraglutide (Saxenda)—may lead to substantial skeletal muscle loss.
Skeletal muscles serve two critical functions: they support bodily structure and movement while also playing a vital role in metabolism. These muscles help maintain balance, posture, and overall strength. Furthermore, they act as a reservoir for amino acids, essential for the body’s response to stress, recovery from trauma, and management of infections. Additionally, skeletal muscles regulate blood glucose levels and synthesize glutamine, crucial for immune function.
Research underscores a concerning trend: individuals who undergo rapid weight loss experience a greater reduction in muscle mass compared to those who lose weight gradually. With GLP-1 receptor agonists proving effective for quick weight loss, researchers from the Pennington Biomedical Research Center at Louisiana State University, along with colleagues from the University of Alberta and McMaster University in Canada, published a commentary in the prestigious journal The Lancet outlining these concerns.
Findings suggest that muscle loss attributed to GLP-1 receptor agonists can range from 25% to 39% of the total weight lost over periods of 36 to 72 weeks, based on declines in fat-free mass, which includes both lean and skeletal muscle mass. In contrast, traditional calorie-restriction methods typically lead to fat-free mass losses of only 10% to 30%.
“This significant muscle loss is largely due to the extent of weight reduction rather than the specific effects of GLP-1 receptor agonists,” the researchers noted, emphasizing that this hypothesis warrants further investigation. They highlighted that the rate of muscle mass decline observed in patients using these drugs far exceeds what is typically associated with age-related muscle loss.
The implications of rapid muscle loss are alarming. Research has established that reduced muscle mass is linked to compromised immunity, an elevated risk of infections, slower wound healing, decreased physical function, diminished quality of life, and shorter life expectancy.
“While evidence regarding GLP-1 receptor agonists remains limited, findings from studies on bariatric and metabolic surgeries suggest that muscle loss does not necessarily equate to a loss of strength,” the researchers stated. “However, strength is just one facet of muscle significance. Muscles have critical metabolic roles beyond mere movement and physical power—functions that are frequently overlooked in discussions about weight loss and muscle mass.”
The authors of the commentary advocate for a comprehensive approach to weight loss treatment, emphasizing the importance of integrating GLP-1 receptor agonists with exercise and nutritional strategies to safeguard muscle mass.
“We must remain vigilant about the side effects linked to new weight-loss medications, particularly as individuals may consume fewer calories and, consequently, miss essential vitamins and minerals,” said Dr. Steven Heymsfield, a professor of metabolism and body composition at PBRC and the senior author of the commentary. “It’s important to recognize that weight loss involves not only fat reduction but also muscle loss. Our focus should be on managing this muscle loss through adequate protein intake alongside an optimal exercise regimen.”
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