The analysis crew offers genetic proof that GLP-1 receptor agonists are related to a discount in each fats and muscle, and the relative discount is larger in fats than in muscle. Credit score: Diabetes, Weight problems and Metabolism (2025). DOI: 10.1111/dom.16171
Diabetes and weight problems have turn into urgent well being points worldwide. Glucagon-like peptide-1 (GLP-1) receptor agonists, a category of medicines broadly used within the remedy of sort 2 diabetes (T2D), have proven important effectiveness in each reducing blood sugar ranges and aiding weight reduction attributable to their distinctive pharmacological mechanisms.
A analysis crew from the College of Public Well being, within the LKS College of Drugs of the College of Hong Kong (HKUMed) assessed the influence of GLP-1 receptor agonist in weight reduction by means of genetic research, aiming to grasp whether or not the usage of these medicines reduces weight attributable to muscle or fats mass loss.
This genetic research revealed that GLP-1 receptor agonists cut back weight by lowering extra fats mass than muscle mass. The analysis findings had been revealed within the journal Diabetes, Weight problems and Metabolism.
GLP-1 receptor agonists are pharmaceutical therapies primarily for T2D and, extra not too long ago, weight problems. They operate by mimicking the motion of GLP-1 hormone, which performs an important position in stimulating insulin secretion, inhibiting glucagon secretion, and delaying gastric emptying to suppress urge for food, thereby regulating blood sugar ranges and leading to weight reduction.
Their utility as a pharmacological intervention for weight discount has gained recognition worldwide; nevertheless, considerations have been raised over whether or not GLP-1 receptor agonists cut back weight (typically measured by physique mass index, or BMI) primarily by way of muscle mass loss, which might result in bodily frailty or sarcopenia.
To check how GLP-1 receptor agonists have an effect on muscle and fats, the HKUMed analysis crew used genetic knowledge of greater than 800,000 European individuals from totally different genome-wide affiliation research (GWAS). They recognized a selected genetic variant (rs877446) linked to decrease BMI that mimicked the impact of GLP-1 receptor agonists.
The crew examined the impact of this variant on several types of lean mass, together with appendicular lean mass, whole-body fat-free mass, and trunk fat-free mass, in addition to numerous measures of physique fats, corresponding to whole-body fats mass, trunk fats mass, trunk fats proportion, physique fats proportion, and waist-to-hip ratio.
The analysis crew discovered that individuals with genetic make-up mimicking the impact of GLP-1 receptor agonists results in reductions in each lean mass (whole-body fat-free mass and trunk fat-free mass) and physique fats (whole-body fats mass, trunk fats proportion and physique fats proportion). Particularly, for every unit discount in BMI, whole-body fats mass decreases by about 7.9 kg, whereas muscle mass reduces by about 6.4 kg.
This means that GLP-1 receptor agonists result in better discount in total physique fats than that in muscle mass, leading to an total physique fats proportion lower of round 4.5%. This helps the effectiveness of GLP-1 receptor agonists in lowering fats greater than muscle.
This research clarifies the controversy relating to the impact of GLP-1 receptor agonists on physique composition as a weight-management remedy, and showcases how a genetic strategy can improve our understanding of how medicines work.
“This study highlights the use of genetics in understanding medication effects, especially when corresponding clinical experimental evidence is limited,” mentioned Professor Ryan Au Yeung Shiu-lun, Assistant Professor within the College of Public Well being, HKUMed. “Genetic insights can guide us in making informed decisions about treatments and their impact on health.”
“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,” remarked Dr. Dipender Gill, Medical Analysis Fellow within the Division of Epidemiology and Biostatistics on the College of Public Well being of Imperial Faculty London, a senior writer of the research.
Extra data:
Yiwen Liang et al, Relative results of genetically proxied glucagon‐like peptide‐1 receptor agonism on muscle and fats mass: A Mendelian randomization research, Diabetes, Weight problems and Metabolism (2025). DOI: 10.1111/dom.16171
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Research finds GLP-1 receptor agonists goal fats over muscle for weight reduction (2025, February 24)
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