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Genetic Insights Indicate That GLP-1 Receptor Agonists for Diabetes Primarily Promote Weight Loss by Targeting Fat Mass Over Muscle Mass

Photo credit: www.sciencedaily.com

The global rise in diabetes and obesity has prompted significant concern among health professionals. Medications known as glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as vital tools in the management of type 2 diabetes (T2D) and have recently gained attention for their potential role in weight loss. A research team from the School of Public Health at the LKS Faculty of Medicine, University of Hong Kong (HKUMed), conducted a genetic study to explore how these medications impact body composition, specifically examining whether weight loss stemmed from a decrease in fat or muscle mass. Their findings, published in Diabetes, Obesity and Metabolism, indicated that GLP-1 receptor agonists primarily reduce fat mass while preserving muscle mass.

GLP-1 receptor agonists function by mimicking the GLP-1 hormone, which is instrumental in insulin secretion and appetite regulation. By inhibiting glucagon release and slowing gastric emptying, these medications not only help manage blood sugar levels but also contribute to weight reduction. The increasing popularity of GLP-1 receptor agonists underscores their potential as a pharmacological intervention for obesity. However, a critical question has arisen regarding whether weight loss from these medications could lead to muscle atrophy, which may increase the risk of frailty and other health issues.

In their investigation, the HKUMed team utilized genetic data from over 800,000 participants of European descent, obtained from various genome-wide association studies (GWAS). They focused on a particular genetic variant (rs877446) associated with lower body mass index (BMI) that simulates the effects of GLP-1 receptor agonists. The researchers assessed this variant’s influence on different types of lean body mass and various fat metrics, including overall fat mass, trunk fat mass, and body fat percentages.

The results revealed that the genetic variant associated with GLP-1 receptor agonist effects indeed led to reductions in both lean mass and fat mass. Specifically, the findings indicated that a decrease of one unit in BMI correlates to a loss of approximately 7.9 kg of fat mass and a reduction of about 6.4 kg in muscle mass. This suggests that the weight-loss effects of GLP-1 receptor agonists are more pronounced in terms of fat reduction, yielding an average drop in overall body fat percentage of around 4.5%.

This research offers clarity regarding the impact of GLP-1 receptor agonists on body composition during weight management therapies, highlighting the role of genetic studies in augmenting our understanding of medication mechanisms.

‘These findings underscore the significant role of genetic research in elucidating how medications influence health outcomes, particularly in areas where clinical data may be sparse,’ stated Professor Ryan Au Yeung Shiu-lun, an Assistant Professor at HKUMed. ‘Understanding the genetic underpinnings of medication effects can significantly inform treatment decisions.’

Dr. Dipender Gill, a Clinical Research Fellow from Imperial College London’s Department of Epidemiology and Biostatistics and a senior author of the study, commented on the benefits of leveraging large-scale genetic data. ‘This approach allows for rapid and cost-efficient insights into drug mechanisms, thereby enhancing future clinical studies and improving patient care outcomes,’ he remarked.

About the research team The study was led by Professor Ryan Au Yeung Shiu-lun from HKUMed’s School of Public Health, with contributions from Dr. Dipender Gill of Imperial College London. The initial author was Liang Yiwen, a PhD candidate at HKUMed. Additional members included Professor Eric Wan Yuk-fai, Dr. Luo Shan, and Professor Cheung Ching-lung, all affiliated with prestigious departments within HKUMed.

Source
www.sciencedaily.com

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