A new genetic study has confirmed that glucagon-like peptide-1 GLP-1 Receptor agonists—widely used to treat type 2 diabetes (T2D) and obesity—primarily promote fat loss rather than muscle loss. Researchers from the School of Public Health at the LKS Faculty of Medicine, University of Hong Kong (HKUMed), conducted the study using genetic data from over 800,000 European participants. Their findings, published in Diabetes, Obesity, and Metabolism, clarify concerns about whether these medications contribute to physical frailty by reducing muscle mass.
Understanding GLP-1 Receptor Agonists and Their Role in Weight Loss
GLP-1 receptor agonists mimic the GLP-1 hormone, which regulates blood sugar levels and suppresses appetite. These drugs have become a popular pharmacological intervention for weight loss worldwide. However, questions have been raised about whether weight loss from these medications is primarily due to fat reduction or a loss of muscle mass, which could lead to frailty or sarcopenia.
To address this, researchers analyzed a genetic variant (rs877446) linked to lower body mass index (BMI), miming the effects of GLP-1 receptor agonists. They examined its impact on body composition measures, including lean mass (muscle) and various fat-related indicators.
Fat Loss Outpaces Muscle Loss
The study found that participants with genetic profiles similar to those influenced by GLP-1 receptor agonists experienced reductions in lean mass and body fat. However, fat loss was more significant. For each unit reduction in BMI:
- Whole-body fat mass decreased by approximately 7.9 kg
- Muscle mass decreased by approximately 6.4 kg
- Overall body fat percentage dropped by 4.5%
These results confirm that GLP-1 receptor agonists reduce more fat than muscle, reinforcing their effectiveness as a weight-loss treatment without significantly increasing the risk of frailty.
Genetics Provide Valuable Insights into Medication Effects
“This study highlights the use of genetics in understanding medication effects, especially when corresponding clinical experimental evidence is limited,” said Professor Ryan Au Yeung Shiu-lun, Assistant Professor at HKUMed. “Genetic insights can guide us in making informed decisions about treatments and their impact on health.”
Dr. Dipender Gill, Clinical Research Fellow at the School of Public Health of Imperial College London, emphasized the broader implications of using genetic data in drug research. “The availability of large-scale human genetic association data allows us to gain valuable insights into drug target effects in a timely and cost-efficient manner. This approach can greatly inform further clinical studies and improve patient outcomes.”
The study not only resolves concerns about muscle loss with GLP-1 receptor agonists but also highlights the potential of genetic research to enhance understanding of drug effects, paving the way for more precise and effective treatment strategies.
Reference: Yiwen Liang, Shan Luo, Eric Yuk Fai Wan, Ching Lung Cheung, Dipender Gill, Shiu Lun Au Yeung. Relative effects of genetically proxied glucagon‐like peptide‐1 receptor agonism on muscle and fat mass: A Mendelian randomization study. Diabetes, Obesity and Metabolism, 2025.
