DIABETES and obesity remain major global health concerns, with researchers continuously seeking effective treatments. A recent genetic study has provided new insights into how glucagon-like peptide-1 (GLP-1) receptor agonists aid weight loss. The study revealed that these medications reduce weight primarily by lowering fat mass rather than muscle mass.
GLP-1 receptor agonists are widely used in the treatment of Type 2 diabetes (T2D) and, more recently, obesity. These medications work by mimicking the GLP-1 hormone, which stimulates insulin secretion, suppresses appetite, and slows gastric emptying. While effective in promoting weight loss, concerns had been raised about whether they primarily reduce muscle mass, potentially leading to frailty or sarcopenia.
To investigate this, the research team analysed genetic data from over 800,000 European participants in various genome-wide association studies (GWAS). They identified a genetic variant (rs877446) associated with lower body mass index (BMI) that mimicked the effects of GLP-1 receptor agonists. By examining its influence on different Types of lean and fat mass, they assessed how these medications impact body composition.
Findings from the study showed that participants with genetic traits simulating the effects of GLP-1 receptor agonists experienced reductions in both lean mass and body fat. However, the decrease in fat mass was more pronounced. For every unit reduction in BMI, whole-body fat mass decreased by approximately 7.9 kg, while muscle mass declined by about 6.4 kg. This resulted in an overall reduction of body fat percentage by around 4.5%.
These results address previous concerns about the effects of GLP-1 receptor agonists on body composition, affirming their efficacy in reducing fat more significantly than muscle mass.
‘This study highlights the use of genetics in understanding medication effects, especially when corresponding clinical experimental evidence is limited,’ said the authors. ‘Genetic insights can guide us in making informed decisions about treatments and their impact on health.’
This research underscores the potential of GLP-1 receptor agonists as a safe and effective option for weight management, reinforcing their role in combating obesity and related health complications.
Reference
Liang Y et al. Relative effects of genetically proxied glucagon-like peptide-1 receptor agonism on muscle and fat mass: a Mendelian randomization study. Diabetes Obes Metab. 2025;DOI:10.1111/dom.16171.
