Genes could predict weight-loss jab effectiveness – study

Variants in specific gene may predict whether people are more likely to suffer side effects linked to the jabs

The finding could help explain why some people appear to lose weight more quickly than others while taking the drugs and why some appear more vulnerable to side effects such as nausea and vomiting. File picture

A person’s genes could play a role in how effective weight-loss jabs are, according to a new study.

Experts found that variants in a specific gene could also predict whether people are more likely to suffer side effects linked to the jabs.

The finding could help explain why some people appear to lose weight more quickly than others while taking the drugs and why some appear more vulnerable to side effects such as nausea and vomiting.

Researchers said the finding, published in the journal Nature, could one day help doctors deliver precision medicine to people trying to lose weight.

The study examined data from almost 28,000 people registered to the genetics website 23andMe and self-reported data on their use of GLP-1 receptor agonist weight-loss treatments including semaglutide, such as Wegovy, and tirzepatide, also known as Mounjaro.

Using genetic data, researchers found that variations in two genes involved with hormones in the gut, which regulate appetite and digestion, could play a role in how these drugs work.

One, the GLP1 receptor variant rs10305420, was associated with a slightly greater decrease in body mass index (BMI) among people taking GLP-1 drugs.

Another, rs1800437 in the gastric inhibitory polypeptide receptor gene, was linked with side effects of nausea and vomiting in people taking tirzepatide, but was not associated with how much weight they lost.

The researchers, led by experts from 23andMe and the University of Copenhagen, said these genetic differences may partially account for differences in weight loss.

Other non-genetic factors play a role, including gender, age, and which treatment a person takes.

“Our study detected a robust genetic association with GLP-1 medication weight loss efficacy and associated side effects,” the authors wrote.

They stressed that the effect was “modest” as they called for future studies to explore the role of genetics in these treatments further.

Marie Spreckley from the University of Cambridge said the study “provides biologically plausible evidence that variation in the drug target itself (GLP1R) and related pathways (GIPR) contributes to inter-individual variability in response.

“However, the magnitude of these genetic effects is small in clinical terms.

“Importantly, non-genetic factors such as sex, drug type, dose, and duration appear to explain a substantially larger proportion of variability.” 

Ms Spreckley added: “In terms of how this fits with the wider evidence, it reinforces that while there is substantial variability in response to GLP-1 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 towards 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.”