Scientists have discovered that genetic variations may help explain why weight-loss jabs work better for some people than others. A study of nearly 28,000 patients found that differences in two genes involved in gut hormone pathways could account for varying weight-loss results or side-effects when taking glucagon-like peptide 1 (GLP1) medicines.
The findings, published in the journal Nature on Wednesday, could support future efforts to use genetic information when making treatment choices for obesity. GLP1 receptor agonists, including semaglutide (Wegovy) and tirzepatide (Mounjaro), mimic natural gut hormones to regulate appetite, insulin release and digestion.
Researchers from 23andMe studied data from 27,885 patients on GLP1 drugs. They found that the GLP1 receptor variant rs10305420 was associated with slightly more weight loss in carriers, while another variant, rs1800437, was linked to nausea and vomiting in those taking tirzepatide but not to weight loss.
However, the overall impact of genetics was modest. Marie Spreckley, an obesity expert at the University of Cambridge, said the study provided plausible evidence but noted that non-genetic factors such as sex, drug type, dose and duration explained a substantially larger proportion of variability.
“Behavioural, clinical and treatment-related factors remain the dominant drivers of outcomes,” she said. “The evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice.”
