Cheng Wong

Researchers from the University of Hong Kong have discovered through genetic research that the diabetes drug GLP-1 helps people lose weight mainly by decreasing fat rather than muscle.

GLP-1 receptor agonists are medications for type 2 diabetes and obesity that mimic the GLP-1 hormone in the body.

They work by inhibiting glucagon secretion, delaying gastric emptying, and suppressing appetite, which helps regulate blood sugar levels and promote weight loss.

But concerns have been raised over whether these medications reduce weight mainly via muscle mass loss, which could lead to physical frailty or sarcopenia.

Led by assistant professor Ryan Au Yeung Shiu-lun from the School of Public Health of HKUMed and clinical research fellow Dipender Gill from the department of epidemiology and biostatistics at the School of Public Health of Imperial College, the HKUMed research team used genetic data from over 800,000 Europeans across various genome-wide association studies.

The researchers identified a specific genetic variant, rs877446, linked to a lower body mass index, producing effects similar to those of GLP-1.

They analyzed how this variant influenced various forms of lean mass, including appendicular lean mass, total fat-free mass, and trunk fat-free mass.

Also, they assessed several body fat metrics: total fat mass, trunk fat mass, trunk fat percentage, body fat percentage, and waist-to-hip ratio.

They found that participants with a genetic makeup mimicking the effect of GLP-1 receptor agonists experienced reductions in both lean mass and body fat - losing about 6.4 kg and 7.9 kg, respectively - indicating the drug results in a greater reduction in fat compared to muscle mass.

"This study highlights the use of genetics in understanding medication effects, especially when clinical experimental evidence is limited," said Au Yeung.

"Genetic insights can guide us in making informed decisions about treatments and their impact on health," he added.

Gill said: "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 clinical studies and improve patient outcomes."

The findings were published in Diabetes, Obesity and Metabolism, with Liang Yiwen, a PhD student at the School of Public Health, as the first author.

Ryan Au Yeung, left, says genetics has helped bring about a greater understanding of the effects of medication in the face of limited clinical evidence.

Diabetes drug gets muscle amid 'fat lot of good' claim