Diabetes and obesity are becoming increasingly prevalent health concerns globally. Glucagon-like peptide-1 (GLP-1) receptor agonists, medications widely utilized in managing type 2 diabetes (T2D), have proven to be effective not only in lowering blood sugar levels but also in promoting weight loss through unique pharmacological mechanisms.
A research team from the School of Public Health within the LKS Faculty of Medicine at The University of Hong Kong conducted a genetic study aimed at understanding how GLP-1 receptor agonists influence weight loss. Specifically, they investigated whether these medications result in muscle or fat mass reduction. Their findings were published in Diabetes, Obesity and Metabolism.
Background:
GLP-1 receptor agonists are primarily used to treat T2D but have also gained attention for their efficacy in obesity management. These drugs work by mimicking the effects of GLP-1 hormone, which stimulates insulin secretion, inhibits glucagon release, and delays gastric emptying to suppress appetite—thus regulating blood sugar levels and contributing to weight loss.
However, a concern exists regarding whether these medications achieve their weight-reducing benefits primarily through muscle mass reduction. This could potentially lead to physical frailty or sarcopenia.
Research Method and Findings:
The HKUMed research team employed genetic data from over 800,000 European participants in various genome-wide association studies (GWAS) to examine the impact of GLP-1 receptor agonists on body composition. They identified a specific genetic variant (rs877446) associated with lower BMI that mirrored the effects of these medications.
The team assessed how this genetic variant affected lean mass, including appendicular lean mass and whole-body fat-free mass, as well as various measures of body fat such as whole-body fat mass, trunk fat percentage, and waist-to-hip ratio. Their results indicated that participants with a genetic makeup mimicking GLP-1 receptor agonists experienced reductions in both lean mass (whole-body fat-free mass and trunk fat-free mass) and body fat (whole-body fat mass, trunk fat percentage, and body fat percentage).
Specifically, for every unit decrease in BMI associated with this variant, whole-body fat mass decreased by about 7.9 kg, while muscle mass reduced by approximately 6.4 kg. This suggests that GLP-1 receptor agonists lead to a greater reduction in overall body fat compared to muscle mass, resulting in an overall body fat percentage decrease of around 4.5%. These findings support the efficacy of these medications in reducing fat more than muscle.
Significance of the Research:
This study addresses ongoing debates about GLP-1 receptor agonists’ impact on body composition as a weight management tool and demonstrates how genetic approaches can provide deeper insights into medication effects, especially when clinical evidence is limited. The research highlights the potential of genetics to guide treatment decisions and inform patient health outcomes.
Ryan Au Yeung Shiu-lun, Assistant Professor in the School of Public Health at HKUMed said, “The availability of extensive human genetic data allows us to gain valuable insights into drug target effects quickly and cost-effectively. This method can greatly inform further clinical studies and improve patient care.”
