Specific gene variants can predict how well a person responds to popular weight-loss injections and whether they are likely to suffer debilitating side effects, according to a major new scientific study. The findings suggest a future where genetic screening could help doctors personalise obesity treatment from the outset.
Research led by the genetics company 23andMe and the University of Copenhagen, published in the journal Nature, identified two key genetic differences that influence the body’s reaction to GLP-1 receptor agonist drugs like semaglutide (Wegovy) and tirzepatide (Mounjaro). Analysing data from almost 28,000 individuals who self-reported their use of the medications, scientists found that a variant in the GLP1 receptor gene itself, known as rs10305420, was associated with a slightly greater decrease in body mass index (BMI) for those on the drugs.
The second variant, rs1800437, sits in the gene for the gastric inhibitory polypeptide (GIP) receptor. This variant was linked to a higher likelihood of experiencing nausea and vomiting specifically for users of tirzepatide, but did not affect the amount of weight lost. Both genes are involved with hormones in the gut that regulate appetite and digestion—the very pathways these powerful drugs are designed to target.
How the drugs work and who can access them
The medications at the centre of the research are estimated to be used by around 1.5 million people in the UK. They mimic natural gut hormones released after eating, helping patients feel fuller, reducing appetite, and slowing digestion. In the UK, Wegovy is licensed specifically for weight management, while Mounjaro is approved for both type 2 diabetes and weight management.
Access via the NHS is restricted to patients meeting strict criteria, such as a high BMI with weight-related health conditions. Privately, the treatments are costly, with Wegovy typically ranging from approximately £90 to £250 per month and Mounjaro from around £130 to £350, depending on dose and whether additional support is included.
Gastrointestinal side effects are common for both drugs. These include nausea, vomiting, diarrhoea, and constipation, which often subside after the first few weeks. While their side effect profiles are broadly similar, semaglutide has been linked to slightly higher rates of vomiting and constipation, whereas tirzepatide may cause more injection site reactions.
Genetics is ‘only one part of a complex picture’
Commenting on the Nature study, Dr Marie Spreckley, a research programme manager at the University of Cambridge, said it provides “biologically plausible evidence” that genetic variation contributes to the differing responses seen between patients. However, she stressed the magnitude of the genetic effect was “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,” Dr Spreckley noted. She reinforced that behavioural, clinical, and treatment-related factors remain the “dominant drivers of outcomes.” While the research is a step towards precision medicine, she concluded the evidence is “not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice.”
The study authors themselves described the genetic association as “robust” but “modest,” calling for more research. Reflecting this cautious approach, 23andMe has launched a personalised report for its health service members predicting outcomes and nausea risk, but acknowledges the genetic effects are limited.
Broader research on treatment and support
The genetic findings come amid broader scientific efforts to improve obesity care. Researchers at the University of Copenhagen have discovered a new drug target that activates the NK2R receptor, aiming to lower appetite without causing nausea or muscle loss. They estimate a drug based on this approach could be ready within five years.
Further research led by Dr Spreckley has highlighted a significant lack of robust nutritional guidance for people using weight-loss drugs, leaving them potentially vulnerable to deficiencies as their food intake reduces. This is a particular concern given that an estimated 95% of GLP-1 users in the UK access the medications privately, where comprehensive dietary advice is not always provided.
Additional work from the University of Copenhagen underscores that exercise is key to maintaining weight loss after stopping medication. Their study found participants who exercised while using a GLP-1 agonist kept off more weight after ending treatment than those who did not.