Researchers have pinpointed a group of genetic variants that may shed light on the differing responses individuals have to obesity medications.
One particular variant appears to correlate with greater weight loss from powerful GLP-1 medications, while others seem linked to a heightened risk of side effects, such as nausea. This research, recently published in Nature, is based on data from nearly 28,000 users of the 23andMe DNA-testing service who reported using weight-loss drugs.
Andrea Ganna, a health data scientist at the University of Helsinki, notes that the large sample size lends weight to the findings. However, he emphasizes that the genetic impact on weight loss itself is modest, suggesting it’s unlikely clinicians will use this information in practice.
Co-author Adam Auton, who works at the 23andMe Research Institute, recognizes that while the association with weight loss is limited, the link with side effects is more pronounced.
Significant Variation
Next-generation weight-loss medications mimic hormones that affect appetite and metabolism. For instance, semaglutide mimics a hormone known as glucagon-like peptide-1 (GLP-1), while tirzepatide mimics both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In one study, participants using semaglutide lost an average of 10% of their body weight, with some losing over 25% and others seeing little to no change.
To explore the genetic factors behind this diverse response, the researchers analyzed data from 23andMe participants who answered questions about their experiences with obesity treatments, including the specific drugs used, duration of use, weight loss results, and any side effects experienced. They then examined hundreds of thousands of genetic variants in these individuals’ genomes for potential correlations.
The findings revealed that individuals with one copy of a specific variant in the gene for the GLP-1 receptor lost an average of 0.76 kilograms more over an 8-month treatment period compared to those lacking the variant. Those with two copies of this variant experienced an average weight loss of approximately 1.5 kilograms more.
