Genetics May Explain Varied Results from Weight-Loss Jabs, Scientists Say
Scientists have uncovered how genetics could help clarify why weight-loss injections, such as Wegovy, yield different outcomes for individuals. Data from nearly 28,000 patients indicates that understanding gene variations might enhance obesity treatments in the future.
Study Links Genetic Variants to Drug Response and Side-Effects
Research published in the journal Nature reveals that variations in two genes involved in gut hormone pathways, which control appetite and digestion, may account for differences in weight loss or side-effects when using glucagon-like peptide 1 (GLP1) medications. GLP1 receptor agonists, including semaglutide (branded as Wegovy) and tirzepatide (marketed as Mounjaro), mimic natural gut hormones and are widely used globally to manage obesity.
These drugs help regulate appetite, insulin release, and digestion, yet the reasons behind varying weight loss or side-effects have remained unclear. A team from 23andMe, a nonprofit medical research institute, analyzed data from 27,885 patients on GLP1 drugs. They found that the GLP1 receptor variant rs10305420 was linked to slightly greater weight loss in carriers, while another variant, rs1800437, was associated with nausea and vomiting in those taking tirzepatide, though it did not affect weight loss amounts.
Modest Genetic Impact Compared to Other Factors
The findings suggest genetic differences could contribute to individual responses to weight-loss jabs. However, the overall influence of genetics appears modest, according to the researchers. Marie Spreckley, an obesity expert at the University of Cambridge not involved in the study, noted that it offers plausible evidence for genetic effects on outcomes.
"The magnitude of these genetic effects is small in clinical terms," she said. "Non-genetic factors such as sex, drug type, dose, and duration explain a substantially larger proportion of variability. Genetics adds only a modest incremental contribution."
She emphasized that while the study reinforces variability in GLP1 therapy responses, genetics is just one part of a complex picture. Behavioral, clinical, and treatment-related factors remain the dominant drivers of outcomes. This research marks an important step toward understanding variability and potential precision approaches, but evidence is insufficient to support using genetic information for routine clinical decisions.
