Scientists have discovered how genetics may help explain why weight-loss jabs work better for some people than others. Variations in two genes involved in gut hormone pathways could account for different weight-loss results or side-effects when taking glucagon-like peptide 1 (GLP1) medicines, according to research published in Nature on Wednesday.
Researchers from 23andMe, a nonprofit medical research institute, studied data from 27,885 patients on GLP1 drugs, including semaglutide (marketed as Wegovy) and tirzepatide (Mounjaro). They found that the GLP1 receptor variant rs10305420 was associated with slightly more weight loss in those carrying the variant. Another variant, rs1800437, was linked to nausea and vomiting in people taking tirzepatide but was not associated with how much weight they lost.
The findings suggest genetic differences may contribute to why people respond differently to weight-loss jabs. However, the overall impact of genetics appeared to be modest, the researchers said. Marie Spreckley, an obesity expert at the University of Cambridge who was not involved with the study, said the research provided plausible evidence that genetic variants could affect outcomes, but noted that non-genetic factors such as sex, drug type, dose and duration explain a substantially larger proportion of variability.
“The authors’ model suggests that most of the explained variance comes from these factors, with genetics adding only a modest incremental contribution,” Spreckley said. She added that while the study is an important step toward understanding variability and potential for future precision approaches, the evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice.
