Weight-loss drugs no longer need a needle. The FDA approved a daily semaglutide pill, sold as Wegovy, in December 2025. In April 2026 it approved orforglipron (Foundayo), the first GLP-1 pill that can be taken at any time of day without food or water restrictions. Both launched with self-pay prices from $149 a month for the lowest doses. With millions of new users, one question keeps coming up: can your DNA tell you whether the pill will work for you, or whether you will spend the first weeks nauseous?
The biggest genetic study so far
In April 2026, researchers from the 23andMe Research Institute published in Nature a genome-wide study of 27,885 people who had used GLP-1 drugs such as semaglutide and tirzepatide (Su et al., Nature, 2026). Two genes stood out, and both code for receptors that these drugs act on.
| Gene | Variant | Finding | Size of the effect |
|---|---|---|---|
| GLP1R | rs10305420 (Pro7Leu) | Slightly more weight loss, on semaglutide and tirzepatide | About 0.6% more reduction in BMI per copy, roughly 0.76 kg |
| GIPR | rs1800437 | More vomiting, on tirzepatide only | 1.83 times higher odds of vomiting with the C version |
The GIPR finding makes biological sense. Tirzepatide acts on two receptors, those for GLP-1 and for another gut hormone, GIP. Semaglutide and orforglipron act only on the GLP-1 receptor. A variant in the GIP receptor can therefore only matter for tirzepatide.
Why this does not predict your result
- The effects are small. Less than 1 kg per copy of the variant, against average losses of about 15% of body weight on semaglutide and about 20% on the highest dose of tirzepatide in the main trials (Wilding et al., 2021; Jastreboff et al., 2022). Your dose, how long you stay on the drug, your diet, sleep and activity matter far more.
- Weight was self-reported. Among the 909 participants who also shared medical records, the median drop in BMI in the records (5.8%) was about half of what people reported (11.8%).
- It is one study, run by a company that sells a report based on it. Independent replication is needed, and no health system uses genetics to choose a GLP-1 drug today.
In June 2026, a separate study linked variants in a third gene, PAM, to a weaker blood-sugar response to GLP-1 drugs in people with diabetes. We covered it in why Ozempic does not work for everyone. Consumer DNA chips do not read those PAM variants.
What your DNA can tell you
Your raw data file cannot yet predict your response to a GLP-1 pill. What it can show is how the systems these drugs act on are set in your body:
- FTO and MC4R shape appetite and how full you feel after meals, the feeling GLP-1 drugs amplify.
- TCF7L2 carries the strongest common type 2 diabetes variant, linked to a weaker response of the gut hormones these drugs imitate.
These genes matter most for what happens after the drug. In the STEP 1 trial extension, people regained about two-thirds of the weight they had lost within a year of stopping semaglutide (Wilding et al., Diabetes, Obesity and Metabolism, 2022). Knowing whether your genes push you toward larger portions or toward snacking helps you plan for that moment.
If you start a GLP-1 pill
- Protein at every meal and strength training two or three times a week, to protect muscle while you lose fat.
- Small, slow meals while the dose goes up: nausea is usually worst in the first weeks and after each dose increase.
- Report side effects to your prescriber rather than stopping on your own. The dose and the drug can be adjusted.
- Plan for the long term. Decide with your doctor if, how and when you might stop, and which habits you will keep.
Important: this article is educational and is not medical advice. Never start, stop or change a prescription medicine based on a genetic result.
See your appetite and blood-sugar genes
The Ultimate report reads FTO, MC4R, TCF7L2 and other weight genes from the raw file you already have from 23andMe, AncestryDNA or MyHeritage, together with a pharmacogenomics section on genes that affect common medicines. It does not read GLP1R or GIPR today.
References
- Su QJ, et al. [Genome-wide association study of weight loss and side effects in 27,885 users of GLP-1 medications, 23andMe Research Institute]. Nature. Published 8 April 2026. doi:10.1038/s41586-026-10330-z.
- US Food and Drug Administration. Approval of oral semaglutide (Wegovy) for chronic weight management, 22 December 2025; approval of orforglipron (Foundayo), 1 April 2026.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216.
- Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564.