The effectiveness of blockbuster weight-loss drugs like Wegovy and Mounjaro, and the severity of their side effects, may be significantly influenced by a person’s genetic makeup, according to a landmark new study.
Research published in the journal Nature, which analysed genetic and health data from 27,885 users of GLP-1 medications, has identified specific gene variants that are linked to how much weight a person loses and whether they suffer severe nausea.
The Genetic Key to Weight Loss
The international study, which utilised data from the 23andMe genetic testing database, found that participants lost an average of 11.7% of their body weight over eight months. However, outcomes varied wildly, with some shedding up to 30% and others seeing minimal change.
By scanning millions of genetic markers, scientists pinpointed a variant known as rs10305420 in the GLP1 receptor gene (GLP1R). According to the study’s authors, individuals carrying this variant lost an estimated additional 0.76kg per copy. Those fortunate enough to possess two copies could see this benefit doubled.
Professor Ruth Loos from the University of Copenhagen, who wrote about the research, stated: “People lose more weight if they have this variant.”
However, the distribution of this genetic advantage is not equal across populations. The research team found that among people of European ancestry, 64% carry one copy and 16% carry two. In stark contrast, only 7% of African Americans carry a copy, highlighting how ethnic background can influence treatment response.
A Genetic Link to Severe Side Effects
Intriguingly, the same study revealed a darker side to genetic predisposition. It identified a separate variant, rs1800437, specifically associated with adverse reactions to the drug tirzepatide, marketed as Mounjaro.
This variant could cause up to 1% of patients on the medication to endure severe vomiting, a reaction nearly 15 times worse than typical. Notably, this strong link to nausea and vomiting was not observed in users of semaglutide (Wegovy/Ozempic). Professor Loos confirmed the dual nature of the first variant, noting it was “associated with weight loss, which was also associated with nausea.”
Despite these findings, experts caution that the direct genetic influence remains modest in clinical terms. Dr Marie Spreckley from the University of Cambridge emphasised that non-genetic factors like the specific drug type, dosage, and treatment duration explain a far larger share of outcome variability.
The UK context for these medications is one of explosive growth and high demand. The market for GLP-1 drugs is vast, with the UK sector alone projected to grow from an estimated $1.3bn in 2025 to over $3.7bn by 2033. As of early 2025, an estimated 1.6 million adults in Great Britain had used GLP-1 or similar medications for weight management in the past year, with most accessing them privately through online pharmacies where prices can range from £130 to over £375 per month.
On the NHS, access is stricter. Semaglutide (Wegovy) is approved for a maximum of two years through Specialist Weight Management Services for those with a BMI of at least 35 and weight-related health issues. Tirzepatide (Mounjaro), approved in late 2024, is being rolled out with a phased approach prioritising those with the highest clinical need.
Beyond genetics, a complex web of factors determines success. Previous research indicates women are more than twice as likely as men to lose 15% of their body weight on Mounjaro. Younger patients, and those who are white or Asian, also tend to achieve greater weight loss, though the reasons are unclear.
Professor Naveed Sattar, a metabolic health expert from the University of Glasgow, offered a measured perspective on the new genetic findings: “Overall, these findings are scientifically interesting, but they are a long way from changing clinical practice.” He echoed calls from other experts, including Dr G. Caleb Alexander of Johns Hopkins University, for more robust trial data to understand why these drugs fail for a substantial minority of users.
Dr Spreckley reiterated the broader picture, stating that “genetics is only one part of a much more complex picture,” where behavioural, clinical and treatment-related factors are the primary drivers. The study authors themselves acknowledged their findings require replication in further research before they could inform a new era of personalised obesity treatment.