Genetic Study: GLP-1⁣ Agonists Lead to Greater ​Fat Loss Than Muscle Loss

⁢ Updated June‌ 12, 2025
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Glucagon-like‍ peptide-1 ⁤(GLP-1) receptor agonists,⁤ widely used ‌for treating type 2 diabetes ⁣(T2D), have demonstrated effectiveness‌ in ‌lowering blood ​sugar and promoting weight ⁣loss. A new study from the University of‍ Hong kong (HKUMed)‍ examined⁢ how these ‌medications affect body ‌composition, specifically whether weight loss is primarily ​due to ​muscle or fat reduction. The findings, published in Diabetes, Obesity and Metabolism,⁢ indicate⁤ that GLP-1 agonists primarily reduce fat mass.

GLP-1 receptor agonists mimic the GLP-1 hormone,stimulating insulin secretion,inhibiting ‌glucagon‌ secretion,and ​suppressing appetite.This mechanism regulates blood sugar and leads to ⁣weight loss.⁤ Concerns have arisen about whether⁢ these agonists reduce weight mainly thru muscle loss, potentially causing frailty. The HKUMed team used ⁤genetic data⁣ from over 800,000 European participants ‌to ⁢investigate ‍this.

Researchers identified a genetic variant ‍(rs877446) linked to lower BMI, mirroring ‍the‍ effects of GLP-1 agonists. They analyzed the⁣ variant’s impact on⁤ lean mass and body ​fat. The study revealed ⁢that individuals with this genetic makeup experienced reductions⁢ in both⁣ lean mass and body fat. For each unit decrease in BMI, ⁣body ⁣fat decreased ​by approximately 7.9 kg, while muscle mass decreased by⁢ about 6.4‍ kg.This⁢ suggests that GLP-1⁣ receptor agonists lead to a greater reduction in body fat, decreasing overall ⁤body fat percentage⁣ by around 4.5%.

The study clarifies ⁤the effect of GLP-1 receptor agonists ⁣on body composition⁢ during weight ⁤management and demonstrates how a genetic‌ approach can enhance understanding of 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.”

“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, ⁤Clinical Research⁢ Fellow at Imperial College London.

What’s next

Further ⁤research will explore the long-term effects of GLP-1 receptor agonists on body composition and overall health,potentially leading to more⁢ tailored treatment strategies for obesity ‍and ‌type 2 diabetes.