Weight-loss drugs like semaglutide and tirzepatide may help shrink waistlines, but new research shows they fail to boost fitness and can cause serious muscle loss, potentially undermining the long-term health benefits of slimming down.
For all of their pluses, we know that a major side effect of the popular GLP-1RA injectable weight loss drugs is that the rapid and significant weight loss they produce is accompanied by a notable loss of fat-free mass, or muscle.
New research led by the University of Virginia Health (UVA Health) has critically examined the effects of popular GLP-1 receptor agonist drugs (GLP-1RAs) and dual GLP-1/GIP receptor agonists (GLP-1/GIPRAs), such as semaglutide and tirzepatide, on cardiorespiratory fitness and muscle health.
“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 lead and corresponding author Zhenqi Liu, MD, Professor of Medicine and Professor of Diabetes at the UVA School of Medicine. “This is a serious concern. Muscle, especially axial muscle, is essential for posture, physical function and overall well-being.
“Losing lean body mass can increase the risk of cardiovascular disease, all-cause mortality and diminished quality of life. We need to make sure that patients prescribed these medications aren’t already at risk for malnutrition or low muscle mass.”
While regular age-related muscle loss (sarcopenia) is around 8% per decade, the loss induced by these medications can account for 25% to 40% of the total weight lost. The researchers set out to better understand the potential long-term consequences of this muscle loss, so they reviewed the available data on the medications’ effects on cardiorespiratory fitness (CRF).
CRF, also known as cardiovascular fitness, refers to the body’s ability to deliver oxygen to skeletal muscles for the energy production required during physical activity. The gold-standard measure of CRF is maximal oxygen consumption, or VO2max. Higher VO2max values indicate better CRF, reflecting the body’s ability to use oxygen efficiently – that is, take it from the air, perfuse it into the bloodstream and deliver it to the tissues – during exercise. Why is CRF so important? Because it’s been shown to be a stronger predictor of mortality than weight alone.
“Cardiovascular fitness is a potent predictor of all-cause and cardiovascular mortality risk across a range of populations, including obesity, diabetes and heart failure,” said Siddhartha Angadi, PhD, associate professor of kinesiology at UVA’s School of Education and Human Development, and the study’s co-corresponding author. “In a recent study by our group that examined mortality outcomes from almost 400,000 individuals across the world, we found that CRF was far superior to overweight or obesity status for predicting the risk of death. In fact, once CRF was factored in, body weight failed to predict the risk of mortality. This is why it’s so important to understand the effects of this new class of drugs on it.”
In the present study the researchers found that while these drugs induced considerable weight loss, a substantial portion of this weight loss came from muscle, which is problematic. Despite benefits to some cardiovascular measures and (obviously) weight loss, these drugs didn’t improve VO2max. They are urging further research to be undertaken to better understand the effects of the drugs and ensure patients get the best possible outcomes.
Newer iterations of injectable weight loss drugs appear not to have the same drastic effect on muscle mass, but they are still undergoing clinical trials. For the moment, the researchers are urging individuals taking or considering taking GLP-1RAs or dual GLP-1/GIPRAs to speak with a medical professional about the issue of muscle loss.
“This is an area of active research, and we are hopeful that better solutions are coming soon,” said Liu. “But for now, it is important that patients prescribed GLP-1 drugs have conversations with their healthcare providers about strategies to preserve muscle mass. The American Diabetes Association recommends screening for malnutrition and low muscle mass risk before starting these medications and promoting adequate protein intake and regular exercise throughout treatment."
Additionally, further study is needed to examine whether exercising while taking GLP-1 medication affects cardiovascular fitness.
“Finally, exercise training during GLP-1 therapy remains to be assessed in its ability to preserve or improve VO2max during GLP-1 therapy,” Angadi said.
The study was published in The Journal of Clinical Endocrinology & Metabolism.
Source: UVA Health