Genetics reveal why people respond differently to GLP-1 weight-loss drugs

In just a few years, weight-loss medications based on GLP-1 (glucagon-like peptide-1) have transformed the treatment of obesity. Millions of adults worldwide have now used these drugs, and the number is expected to increase exponentially. The degree of weight loss these drugs induce often exceeds 20% of body weight, a level previously unimaginable1,2. However, responses vary considerably. Although most participants in clinical trials lose more than 10% of their body weight, about one in ten achieve less than 5% and are considered non-responders. Tolerability also differs substantially, with at least one in three users experiencing adverse events, such as nausea, vomiting, diarrhoea or constipation, whereas others report minimal or no events. Writing in Nature, Su et al.3 report that genetic differences between users might help to explain some of the variability in responses to GLP-1-based anti-obesity medications.

doi: https://doi.org/10.1038/d41586-026-00905-1

References Wilding, J. P. H. et al. N. Engl. J. Med. 384, 989–1002 (2021). Jastreboff, A. M. et al. N. Engl. J. Med. 387, 205–216 (2022). Su, Q. J. et al. Nature https://doi.org/10.1038/s41586-026-10330-z (2026). Vujkovic, M. et al. Nature Genet. 52, 680–691 (2020). Saunders, G. R. B. et al. Nature 612, 720–724 (2022). Manne-Goehler, J. & Franco, J. BMJ 390, r1606 (2025). Karczewski, K. J. et al. Nature Genet. 57, 2408–2417 (2025). Yengo, L. et al. Hum. Mol. Genet. 27, 3641–3649 (2018). German, J. et al. Nature Med. 31, 2269–2276 (2025). Download references

Competing Interests R.J.F.L. is at the Novo Nordisk Foundation Center for Basic Metabolic Research, an independent research centre at the University of Copenhagen that is partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF23SA0084103 and NNF18CC0034900).

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