Why do GLP-1s work so well for some people and not others?
Across 27,885 people tracked on GLP-1s, the typical loss was around 12 percent of body weight. The spread around that average is enormous: in a large semaglutide trial, about a third of patients lost less than 5 percent or gained weight, while roughly one in twenty lost more than a quarter of their body weight. Part of that spread is written in your DNA.
Range of weight loss seen between individuals on the same GLP-1
Nausea and GI side effects are the most common reason people stop GLP-1s
GLP1R and GIPR are the two genes most tied to how you respond
Dose, diet, activity, and other medications all matter. Genetics is one lever you cannot change but can plan around. Knowing your GLP1R and GIPR results up front helps set realistic expectations and can inform how quickly you move up in dose.
Your genetics, your GLP-1 response
Based on recent GLP-1 pharmacogenetics research, including a 2026 study of GLP1R and GIPR variants published in Nature. Two common variants change how strongly your body responds to these drugs.
Su QJ, et al. Genetic predictors of GLP1 receptor agonist weight loss and side effects. Nature 653:770-775 (2026). The effect was measured most precisely in people of European ancestry, where the variant is most common.
The same variant, two different drugs
Odds of moderate-to-severe vomiting for carriers of the GIPR Gln354 variant, compared with non-carriers on the same drug.
Odds of vomiting vs non-carriers, with 95% confidence interval
Tirzepatide is sold as Mounjaro and Zepbound; semaglutide as Ozempic and Wegovy. This is the most directly useful GLP-1 result we report: if tirzepatide nausea is a problem for you, this variant does not affect semaglutide. Bars show the 95% confidence interval, and semaglutide's crosses "no change", which is why we report it as no measurable effect rather than as a benefit.
View as a table
| Drug | Odds vs non-carriers | 95% CI | Significance |
|---|---|---|---|
| Tirzepatide | 1.85× | 1.54 to 2.24 | P = 1.1 × 10-10 |
| Semaglutide | 0.93× | 0.85 to 1.04 | Not significant (P = 0.23) |
Derived from the reported effect-allele odds ratios in Su QJ et al., Nature 653:770-775 (2026), Figure 2c, expressed here for the Gln354 risk allele.
GLP1R encodes the GLP-1 receptor, the direct target of every GLP-1 drug. A common signal-peptide variant changes how efficiently the receptor reaches the cell surface, and with it the strength of the response. It matters for all GLP-1s, including semaglutide and tirzepatide.
GIPR encodes the GIP receptor. It only matters for drugs that hit the GIP receptor, which means tirzepatide (Mounjaro, Zepbound) but not semaglutide. This is the most directly actionable GLP-1 genetic result we report.
These are research-backed signals, not formal CPIC or FDA guidelines. There is no contraindication here. Most people do well on GLP-1s. Your results help set expectations and inform how you and your clinician approach titration.
What is in your GLP-1 report
Clear, personalized results you can read in minutes and share with your clinician. Included with the Complete report.
Expected weight loss
How your GLP1R genetics may influence how much weight you lose on GLP-1s.
Nausea and side-effect risk
Your GLP1R and GIPR variants and what they mean for GI side effects, including tirzepatide-specific risk.
Medication guidance
Pharmacogenetic insights for 111 medications, including GLP-1s, so you see the full picture.
Actionable insights
Plain-language results you can bring to a conversation with your healthcare provider.
How it works
No blood draw, no clinic visit, no prescription. Use the genetic data you already have.
Upload your raw DNA file
Export your file from 23andMe, AncestryDNA, MyHeritage, or upload a whole genome sequencing VCF from any provider.
We analyze your genes
Gene2Rx reads GLP1R and GIPR plus 27 pharmacogenes to build your personalized drug response profile.
Get your report in minutes
Read your GLP-1 results and medication guidance right away, then share them with your clinician.
No doctor required
Get your GLP-1 genetics without a prescription or an appointment.
Results in minutes
No lab wait. Your report is ready almost as soon as you upload.
Affordable
A fraction of the cost of clinical pharmacogenetic panels.
Already have 23andMe, AncestryDNA, MyHeritage, or WGS data?
Turn the genetic data you already have into GLP-1 and medication insights today.
Consumer genotyping arrays and whole genome sequencing VCFs are both supported. GRCh37 and GRCh38 both work. A whole genome sequencing VCF adds $15 per report for the extra computation.
Get your GLP-1 report
Your GLP1R and GIPR results come in the Complete report, alongside every other medication we cover. Upload the DNA data you already have and read it in minutes.
Complete Pharmacogenetics Report
One-time payment. No subscription, no prescription.
- Your GLP-1 results: GLP1R and GIPR, covering semaglutide, tirzepatide, and retatrutide
- Weight-loss response and nausea risk, explained in plain language
- 111 medications across all 33 drug classes, included
- Ready in under a minute, yours to keep and share with your clinician
Uploading a whole genome sequencing VCF adds $15. See exactly what the Complete report covers, or browse the full weight-management drug list.
Not looking for GLP-1 results? We also offer a $5 Starter and $35 Psychiatric report, neither of which includes GLP-1.
Important Disclaimer
Always consult your healthcare provider before making any changes to your medications or dosages.
Direct-to-consumer genetic data is not clinical grade. GLP-1 pharmacogenetic findings are research-backed signals, not formal CPIC or FDA guidelines. The information in our reports should be used only as a conversation starter with your healthcare provider to discuss appropriate clinical laboratory testing.
This report does not diagnose any condition and does not determine whether a GLP-1 medication is right for you. That is a decision for you and your clinician.
GLP-1 genetics questions
What people ask before checking their GLP-1 genetics with Gene2Rx
See how your genetics shape your GLP-1 response
Upload the DNA data you already have and get your personalized GLP-1 report in minutes.
Check your GLP-1 genetics