How well your weight loss drugs work may not depend on dosage, diet or adherence.
In fact, their effectiveness may be entirely out of your control. How well you respond to the drugs could be prewritten into your DNA.
Researchers in California tracking 28,000 people on GLP-1 medications, which include Ozempic, Wegovy and Mounjaro, found they lost an average of 25lbs (11.3kg) over eight months.
But some users lost significantly more weight than others.
To investigate why there was such a discrepancy, researchers analyzed all the participants’ DNA and revealed two genetic variants that may influence how well the drugs work — and how likely they are to cause side effects.
One variant, called rs10305420 is on a gene linked to hunger hormones and was found to boost weight loss.
People who had just one copy of this variant lost 1.7lbs (0.7kg) extra in eight months on average, while those who had two copies lost 3lbs (1.4kg) more on average.
About 64 percent of Europeans have at least one copy of this variant, the scientists said, but it is less common in other groups. Among African Americans, only seven percent have the gene.
Meghan Trainor, 31, looked nearly unrecognizable after she revealed she had lost 60lbs in a year. She has revealed that she has taken Mounjaro. The singer is pictured above in 2020 (left) and in November 2025. There is no evidence that she has genes that could have made the drugs more or less effective
Researchers said the gene may have boosted weight loss because it caused the body to have more receptors for GLP-1, making the drugs more effective.
The team also found a second variant, called rs1800437, that they said could influence how likely someone was to experience side effects.
Common side effects of weight loss drugs include nausea, constipation, vomiting and abdominal discomfort.
The study found, among those taking tirzepatide, the active drug behind Mounjaro and Zepbound, people with this variant were more likely to report side effects.
In people who had two copies of both variants, the researchers found they were 15 times more likely to suffer from vomiting while on the medications.
Suffering from side effects can also make the drugs less effective, because they raise the likelihood of someone missing a dose or quitting the medication.
It was not clear how many people carry the variant linked to side effects, but fewer than one percent of people are thought to carry two copies of both variants.
Overall, people are less likely to become unwell on tirzepatide compared to semaglutide, the active drug in Ozempic and Wegovy, the researchers said. But, they warned that, because tirzepatide acts on two systems in the body, rather than one in the case of semaglutide, any mutations could raise the risk of side effects.
Study co-author and genetics researcher Dr Adam Auton told Scientific American that the study’s results — finding genes that may be linked to weight loss drug’s effectiveness — ‘makes perfect biological sense’.
‘The genetic variant we found lands right in this gene [for] the GLP-1 receptor, which happens to be the target for these medications.’
Scientists said that someone’s genetics could make weight loss drugs more effective
Rosie O’Donnell, 63, has lost more than 50lbs within two years while taking Mounjaro, which contains tirzepatide. She is shown above in September 2022 (left) and July last year. There is no evidence that she has genes that could have made the drugs more or less effective
Whoopi Goldberg, 69, said she has lost the weight of ‘two people’. She is shown above in 2019 and after her weight loss. She took Mounjaro. There is no evidence that she has genes that could have made the drugs more or less effective
Dr Ruth Loos, a genetic epidemiologist at the University of Copenhagen who was not involved in the study, said that the extra weight loss was significant.
She wrote in an accompanying article that, although it appeared low overall, it was equivalent to about 10 percent extra weight loss in terms of total bodyweight.
The analysis flagged variants on two genes.
The variant linked to weight loss was found on the GLP1R gene, which encodes for the hunger-satiating GLP-1 hormone, and the variant that was linked to side effects was found on the GIPR gene, with this gene said to help ease side effects.
Semaglutide targets the GLP-1 pathway, which is involved in insulin release, stomach emptying and appetite control.
But tirzepatide targets both GLP-1 and the GIP pathway, which some scientists say is why it is less likely to trigger nausea
The researchers, whose work was published in the journal Nature, said they hoped that their work could help with developing bespoke weight loss medications, helping people lose more weight while on the drugs.
People can find out whether they have these genetic variants using a genetic test.
In the study, researchers from DNA testing platform 23andMe analyzed data from the California-based company’s database.
Overall, participants were obese, 52 years old and 84 percent were female. Nearly 80 percent of respondents were also from a white ethnic background.
More than 15,000 participants were on Ozempic or Wegovy, while nearly 7,000 were on Mounjaro on Zepbound. Another 5,000 were on either compounded semaglutide or tirzepatide.
On side effects, about 20 percent reported experiencing constipation or a loss of pleasure from eating, while 10 percent reported stomach pain.
