Jump to: What the study found | Why the same medication works differently | The variant linked to weight loss | The variant linked to nausea on Mounjaro | The 23andMe consumer report | Limitations to keep in mind | What this means for the UK | Take home message
Two people can take the same GLP-1 medication at the same dose and have very different experiences. One might lose 20% of their body weight with few side effects. Another might lose 6% and experience such severe nausea that they need to stop taking the medication.
A large genetic study published in Nature on 8 April 2026 has identified specific gene variants that help explain why.1
Researchers at the 23andMe Research Institute analysed data from 27,885 people taking GLP-1 medications. They found that a variant in the GLP1R gene is associated with greater weight loss on both semaglutide and tirzepatide.1
A separate variant in the GIPR gene predicts nausea and vomiting specifically in people taking tirzepatide (Mounjaro and Zepbound), but not in people taking semaglutide (Wegovy and Ozempic).1
Across participants, predicted weight loss ranged from 6% to 20% of starting body weight, and the estimated chance of experiencing nausea ranged from 5% to 78%, depending on genetic and clinical factors.2
The genetic effects on weight loss are modest at the individual level. The variant linked to greater weight loss adds an estimated 0.76 kg for each copy of the gene variant a person carries (we inherit two copies of most genes, one from each parent), against a backdrop of average weight loss in clinical trials of 10-15% of body weight.13
These findings don’t change how GLP-1 medications are prescribed today. But they provide the largest-scale evidence to date that variation in medication response is partly influenced by genetics.
Important safety information: This article discusses research into genetic factors that may influence the response to GLP-1 medications. It’s for informational purposes only and isn’t a diagnostic tool. Genetic testing for GLP-1 response isn’t currently available through the NHS. Always consult with your healthcare provider before starting, stopping, or changing any medication.
What the study found
The study was a genome-wide association study (GWAS), a type of research that scans the entire genome for genetic variants linked to a specific outcome.
It was conducted by the 23andMe Research Institute and published in Nature on 8 April 2026.1
The researchers analysed data from 27,885 people who had taken a GLP-1 medication, including semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound).
The cohort was 82.4% female, with a median age of 52; 78.3% were of European ancestry, 12.9% Latino, and 4.2% African American. Median pre-treatment BMI was 35.1 kg/m².1
Participants self-reported their weight loss and side effects.
Two main findings emerged:
- A small change in the GLP1R gene (rs10305420) was significantly associated with greater weight loss. Each copy of the gene was linked to an additional 0.76 kg of weight loss (P = 2.9 × 10⁻¹⁰).1
- Variants in both the GLP1R and GIPR genes were associated with nausea and vomiting. The GIPR variant (rs1800437, p.Glu354Gln) was associated with nausea only in people taking tirzepatide. People who inherit one version of this gene variant are nearly twice as likely to experience vomiting on tirzepatide compared to those who inherit the other version.1
| Gene variant |
What it predicts |
Semaglutide (Wegovy, Ozempic) |
Tirzepatide (Mounjaro, Zepbound) |
| GLP1R (rs10305420) |
Weight loss |
Associated |
Associated |
| GLP1R |
Nausea and vomiting |
Associated |
Associated |
| GIPR (rs1800437) |
Nausea and vomiting |
No association |
Associated |
The research team then built a predictive model that combines genetic data with clinical factors such as age and existing medical conditions.
Using this model, estimated weight loss ranged from 6% to 20%, and nausea risk ranged from 5% to 78%.2
The GLP1R weight loss finding replicated in the All of Us cohort of 4,855 people (P = 0.001), but didn’t replicate in the UK Biobank, though the authors note that statistical power for replication in that cohort was low.1
Why the same medication works differently in different people
GLP-1 medications work by mimicking a hormone called GLP-1 that our body naturally produces in the gut after eating. This hormone signals to the brain that we’re full, slows gastric emptying, and reduces appetite.
The GLP1R gene codes for the receptor that GLP-1 binds to. A variant that changes the structure of this receptor could make the medication bind more or less effectively, which would affect how much weight a person loses.
Tirzepatide (the drug in Mounjaro and Zepbound) works differently from semaglutide because it mimics two hormones rather than one: GLP-1 and GIP. GIP is a separate gut hormone that regulates insulin and appetite.
The GIPR gene codes for the receptor that GIP binds to. This is why the GIPR variant only affects people taking tirzepatide.
Semaglutide doesn’t interact with the GIP receptor, so variations in the GIPR gene don’t influence its response.
In practical terms, if someone is experiencing persistent nausea on Mounjaro, their genetics may make them more susceptible to GIP-related side effects.
Semaglutide, which only acts on the GLP-1 receptor, might be better tolerated in that situation.
The decision to switch medications should always be made with a prescriber based on the full clinical picture, not on genetics alone.
The gene variant linked to weight loss
The GLP1R variant identified in the study (rs10305420) is a small change in the genetic code. A single amino acid in the receptor protein has been swapped for a different one, like changing one letter in a long word.
It’s a small structural change, but it appears to make the receptor more responsive to GLP-1 stimulation.1
Each copy of the variant was associated with an additional 0.76 kg of weight loss.1
We inherit two copies of most genes (one from each parent), so someone with two copies of this variant would be expected to show a more pronounced response than someone with one or none.
The variant doesn’t determine how much weight you lose on its own. The predictive model found that clinical factors, including age, starting weight, and existing medical conditions, also contributed to the overall estimate.2
The predicted range across participants, from 6% to 20% of starting body weight, reflects the combined influence of genetics and these clinical factors.2
The gene variant linked to nausea on Mounjaro
Nausea is the most common side effect of GLP-1 medications. In clinical trials, it typically occurs during dose escalation and resolves for most people within a few weeks.
This study found that a variant in the GIPR gene (rs1800437, also known as p.Glu354Gln) was associated with a higher risk of nausea and vomiting, but only in people taking tirzepatide.1
Tirzepatide activates both GLP-1 and GIP receptors. If a person carries a GIPR variant that affects GIP receptor function, the combined stimulation of both receptors may produce a stronger nausea response than GLP-1 stimulation alone.
People who inherit one version of this gene variant are nearly twice as likely to experience vomiting on tirzepatide compared to those who inherit the other version.
Semaglutide only activates the GLP-1 receptor, so it isn’t affected by GIPR variants. This may help explain why some people who struggle with nausea on Mounjaro find a semaglutide-based medication easier to tolerate, though other factors will also play a role.
The estimated nausea risk across the model ranged from 5% to 78%, depending on the individual’s genetic profile and clinical characteristics.2
The 23andMe consumer report
23andMe has released a report called ‘GLP-1 Medications Weight Loss and Nausea’ for members of its Total Health subscription service.
The report provides individual estimates of expected weight loss and risk of nausea based on a person’s genetic results, age, and medical history.2 This is an early application of pharmacogenomics (using genetic information to predict medication response) to obesity treatment.
The 23andMe report is a consumer product, not a clinical tool. It hasn’t been validated in a randomised clinical trial, and it isn’t part of any prescribing guideline.
No healthcare system currently uses genetic testing to guide GLP-1 prescribing decisions. This study is the earliest stage of that research, not a ready-to-use clinical application.
Limitations to keep in mind
This was a genome-wide association study, not a randomised controlled trial. GWAS studies identify statistical associations between genetic variants and outcomes, but they can’t prove that a specific variant causes a particular response.
The weight loss data were self-reported by 23andMe customers, not measured in a clinical setting.
The authors checked a subset of 909 participants against their medical records and found that participants tended to overstate their weight loss (5.79% measured vs 11.8% self-reported, median BMI change).1
The 23andMe research population skews heavily towards European ancestry (78.3%) and was 82.4% female.1 The findings may not generalise to more diverse populations.
23andMe is a commercial company with a financial interest in genetic health products. The study’s findings directly informed a paid consumer report, which is worth considering when interpreting the results.
The effect sizes are modest. Commenting on the study for the UK Science Media Centre, Dr Marie Spreckley, a postdoctoral researcher at the University of Cambridge specialising in obesity and incretin-based therapies, noted:
“The magnitude of these genetic effects is small in clinical terms. In clinical trials, typical weight loss with these medications is often in the range of around 10-15%, so a difference of less than 1kg per allele is modest.”3
Earlier research has identified the same variants but reached different conclusions.
A 2015 Slovenian study on the same GLP1R variant in women with polycystic ovary syndrome found the opposite: people with the variant lost less weight, not more.
The GIPR variant rs1800437 was previously identified as a partial loss-of-function mutation in a 2019 Chinese type 2 diabetes study.
The authors of the current paper attribute these discrepancies to differences in disease context, smaller sample sizes in earlier studies, and variations in drug type and analytical methods.4
The GLP1R weight loss finding replicated in the All of Us cohort but did not replicate in UK Biobank.1
Pharmacogenomic findings typically require consistent replication across multiple independent cohorts before they can be used to guide clinical decisions.
What this means for the UK
Genetic testing for GLP-1 medication response isn’t available through the NHS or any UK prescriber.
There are no NICE guidelines recommending genetic testing before starting obesity treatment.
The 23andMe Total Health service is a US-based consumer product. It’s accessible online from the UK, but it’s a paid subscription, and the report hasn’t been developed with UK prescribing practices in mind.
The GLP1R weight loss finding from the main study did not replicate in the UK Biobank, though the authors note that the UK Biobank group was too small to reliably detect the effect.1
It illustrates that research results need to be consistently replicated across different populations before they can guide clinical decisions in the UK.
In the UK, GLP-1 prescribing remains guided by clinical factors: licensing, availability, existing health conditions, and how the patient responds once treatment starts.
If you’re taking Mounjaro and experiencing persistent nausea that isn’t improving with dose adjustments, this research offers some scientific context for why that might be happening.
The clinical advice remains the same: speak with your prescriber about whether adjusting your dose or considering a different medication would be appropriate.
Take home message
A study of nearly 28,000 people, published in Nature, provides the largest-scale genetic evidence so far that individual variation in GLP-1 medication response is partly influenced by genetics.
A variant in the GLP1R gene is associated with differences in weight loss, while a variant in the GIPR gene predicts nausea specifically in people taking tirzepatide (Mounjaro), not semaglutide (Wegovy or Ozempic).
These findings help explain why two people on the same medication can have very different experiences, but they don’t change how medications are prescribed today.
The genetic effects are modest at the individual level (less than 1 kg of additional weight loss per copy of the gene variant), and the findings haven’t replicated consistently across populations.
Genetic testing for GLP-1 response isn’t part of any prescribing guideline, and the consumer product based on this research hasn’t been validated in a clinical trial.
If you’re taking a GLP-1 medication and want to get the most from your treatment, the strongest current evidence points to combining medication with structured lifestyle and behaviour change support.
Second Nature’s published research found that members taking semaglutide alongside dietitian-led behaviour change support achieved an average of 19.1% weight loss at 12 months.5
Second Nature's Mounjaro and Wegovy programmes
Second Nature provides Mounjaro or Wegovy as part of our Mounjaro and Wegovy weight-loss programmes.
Why choose Second Nature over other medication providers, assuming you're eligible?
Because peace of mind matters.
We've had the privilege of working with the NHS for over eight years, helping people across the UK take meaningful steps toward a healthier, happier life.
Our programmes are designed to meet people where they are, whether that means support with weight loss through compassionate one-to-one health coaching, or access to the latest weight-loss medications (like Mounjaro and Wegovy) delivered alongside expert care from a multidisciplinary team of doctors, psychologists, dietitians, and personal trainers.
At the heart of everything we do is a simple belief: real, lasting change comes from building better habits, not relying on quick fixes. We're here to support that change every step of the way.
With over a decade of experience, thousands of lives changed, and a long-standing record of delivering programmes used by the NHS, we believe we're the UK's most trusted weight-loss programme.
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References
- Su, Q.J., et al. (2026). Genetic predictors of GLP1 receptor agonist weight loss and side effects. Nature. DOI: 10.1038/s41586-026-10330-z.
- 23andMe Research Institute. (2026). New 23andMe Research Institute study identifies genetic predictors for GLP-1 weight loss efficacy and side effects. Press release, 8 April 2026.
- Science Media Centre. (2026). Expert reaction to paper about genetic predictors of GLP1 receptor agonist weight loss and side effects. Expert reaction, 8 April 2026.
- Loos, R.J.F. (2026). Genetics reveal why people respond differently to GLP-1 weight-loss drugs. Nature News & Views. DOI: 10.1038/d41586-026-00905-1.
- Richards, R., et al. (2025). A remotely delivered, semaglutide-supported specialist weight management program: 12-month outcomes. JMIR Formative Research, 9(1), e72577.
