Shedding Weight, Losing Muscle: Study Links GLP-1 Drugs to Reduced Muscle Mass - Video

Popular weight-loss medications like GLP-1 drugs are helping millions shed significant weight, but they may come with an overlooked downside: a lack of improvement in heart and lung function, a key indicator of long-term health. A new paper published in the Journal of Clinical Endocrinology & Metabolism by researchers from the University of Virginia (UVA) warns that these medications may fail to enhance cardiorespiratory fitness (CRF), despite their other health benefits.

GLP-1 drugs, widely prescribed to treat obesity, type 2 diabetes, and heart failure, are known for improving blood sugar control and reducing short-term heart and kidney-related risks. However, the UVA team found that while patients lose fat, they also experience a substantial loss in fat-free mass — especially muscle — which could impact their cardiovascular health in the long run.

The research team reviewed existing studies on GLP-1 drugs and their impact on cardiorespiratory fitness, which is commonly measured through VO2max — a clinical marker for how well the body uses oxygen during exercise. While GLP-1 medications improved certain heart function metrics, they did not show consistent or meaningful improvements in VO2max.

"Cardiorespiratory fitness is a potent predictor of all-cause and cardiovascular mortality risk across a range of populations, including obesity, diabetes and heart failure," said Angadi, a cardiovascular exercise physiologist with UVA's Department of Kinesiology. "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."

The authors recommend integrating exercise programs and proper nutrition alongside GLP-1 therapy to mitigate muscle loss and improve long-term outcomes. Until more solutions are available, the researchers stress the importance of patient-provider discussions on nutrition, physical activity, and regular screenings for malnutrition and muscle loss risk.

Reference: Zhenqi Liu, Nathan R Weeldreyer, Siddhartha S Angadi. Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness: A Narrative Review. The Journal of Clinical Endocrinology & Metabolism, 2025; DOI: 10.1210/clinem/dgaf335