People who carry variations in two genes linked to appetite and digestion can lose more weight when taking drugs such as Wegovy and Mounjaro to treat obesity, research suggests.
The findings, outlined in the Nature journal, could explain why some people lose far more weight than others and why some have particularly bad side-effects, such as nausea and vomiting, while taking them.
The popular medicines remove feelings of hunger by acting like a natural gut hormone that makes users feel full.
While genes may play a relatively modest role in influencing how well these drugs work, experts say other factors such as your sex, age and even where you come from can also have an impact.
It is thought at least 1.6 million people in the UK have tried weight-loss drugs in the past year, and that number is expected to rise.
Most are being bought privately through online pharmacies. The NHS only offers Wegovy and Mounjaro to a small percentage of people who have obesity and other related health issues.
The percentage of body weight lost when taking weight-loss medication can vary widely. Drug trials suggest 14% weight loss on semaglutide (Ozempic and Wegovy) and 20% on tirzepatide (Mounjaro).
In this study, based on the experiences of 15,000 people taking weight-loss medications, they lost an average of 11.7% of their body weight during roughly eight months of treatment. Some lost 30% of their weight, while others lost little or nothing.
All of those 15,000 had previously signed up for gene-testing by the company 23andMe, which used that data to chart the experiences of people taking weight-loss drugs. By analysing millions of their genetic variants, the researchers found a pattern suggesting a link between some variants and the effectiveness of the drugs.
Professor Ruth Loos, from the University of Copenhagan, who wrote about the research in Nature journal, said: “The study found a genetic variant associated with weight loss, which was also associated with nausea.
“People lose more weight if they have this variant.”
And that extra lost weight amounted to about 0.76kg (1.6 lbs) on average – but those people who carry two copies of the genes can double the amount they lose.
The variant is high in people with European ancestry – 64% carry one copy, while 16% of people carry two copies, she says.
That compares to 7% of African Americans who carry a copy of the gene.
“If you carry the variant, you will lose more weight,” says Prof Loos.
The study found another variant that could be responsible for people experiencing side-effects such as nausea and vomiting when taking tirzepatide (Mounjaro).
And that could mean up to 1% of people taking the drug will have really bad vomiting – nearly 15 times worse than normal.
Prof Loos said the genetic effect, while modest, “is similar to other factors – and not trivial”.
However she said the findings need to be reproduced in other studies and, to date, that has not happened.
For Dr Marie Spreckley, from the University of Cambridge, “genetics is only one part of a much more complex picture”.
She said the main drivers of outcomes are “behavioural, clinical, and treatment-related factors”. So how much daily exercise and healthy eating people do alongside taking the medication, as well as support and advice offered, plus other underlying health issues.
But there are other factors at play too.
Women are more than twice as likely to lose 15% of their body weight on Mounjaro than men, previous research suggests.
Being younger, white or Asian are also thought to be linked to more weight loss – although the reasons are not fully understood.
And the type of medication used, the dose and how long it is taken for have all been linked with greater weight loss.
In the long term, taking genetic and other information together could help guide the choice of which weight-loss drug to use, based on the potential benefits – something called “precision medicine”.
But we are not there yet, said Professor Naveed Sattar, metabolic health expert from the University of Glasgow.
“Overall, these findings are scientifically interesting, but they are a long way from changing clinical practice,” he said.
“What we really need now is more robust trial data to better define the balance of benefits and harms with these and many other emerging newer therapies.”
