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, which regulate appetite and digestion, may help account for different 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 (known by the brand name Wegovy) and tirzepatide (marketed as Mounjaro), are medicines that mimic natural gut hormones.
The drugs, which help regulate appetite, insulin release and digestion, are used by millions of people worldwide to treat obesity. However, the reasons why some lose more weight than others, or why some experience side-effects, have remained elusive.
Researchers from 23andMe, a nonprofit medical research institute, 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 those carrying this variant compared with those who lacked it. Another variant, rs1800437, was associated with 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 it provided plausible evidence that genetic variants could affect outcomes.
“However, the magnitude of these genetic effects is small in clinical terms,” she said. “Importantly, non-genetic factors such as sex, drug type, dose and duration appear to 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.
“In terms of how this fits with the wider evidence, it reinforces that while there is substantial variability in response to GLP1 therapies, genetics is only one part of a much more complex picture. Behavioural, clinical and treatment-related factors remain the dominant drivers of outcomes.
“Overall, this is an important step toward understanding variability and the potential for future precision approaches, but the effects are modest and the evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice.”
