Scientists discover why ozempic may not work for some people
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A hidden genetic quirk may be making some people surprisingly resistant to the benefits of blockbuster GLP-1 diabetes drugs.
– Scientists have identified genetic variants that may make some people less responsive to GLP-1 drugs used to treat Type 2 diabetes. Roughly 10% of the population carries these variants, which appear to cause a mysterious form of “GLP-1 resistance.” In several clinical trials, carriers were significantly less likely to reach healthy blood sugar targets while taking GLP-1 medications.
More than one-quarter of people with Type 2 diabetes now use GLP-1 receptor agonists, a class of medications that includes Ozempic. But new research from Stanford Medicine and international collaborators suggests these widely prescribed drugs may be less effective for some patients because of their genetics.
The study found that about 10% of people carry genetic variants linked to a phenomenon known as GLP-1 resistance. Individuals with these variants appear to produce higher levels of the hormone GLP-1 (glucagon-like peptide-1), which helps regulate blood sugar, yet the hormone does not seem to work as effectively in their bodies.
Researchers focused on blood sugar control and did not reach firm conclusions about weight loss effects. Drugs such as Ozempic and Wegovy are typically prescribed at higher doses for obesity treatment than for diabetes management, and more research is needed to determine whether the same genetic factors influence weight loss outcomes.
Published in Genome Medicine, the study brought together scientists from multiple countries over a period of 10 years. The work included experiments in both humans and mice, along with analyses of data from clinical trials involving diabetes medications.
“In some of the trials, we saw that individuals who had those variants were unable to lower their blood glucose levels as effectively after six months of treatment,” said Anna Gloyn, DPhil, professor of pediatrics and of genetics at Stanford Medicine and one of the study’s senior authors. At that stage, physicians would often consider changing a patient’s treatment plan. Identifying likely responders in advance could help patients reach the most effective therapy sooner and move diabetes care closer to precision medicine, she said.
– Mahesh M. Umapathysivam, Elisa Araldi, Benoit Hastoy, Adem Y. Dawed, Hasan Vatandaslar, Johanna E. Mayrhofer, Peter Lindquist, Pamuditha N. Silva, Algera Goga, Geraldine O. Trüllinger, Svenja Godbersen, Shahana Sengupta, Adrian Kaufmann, Søren Krogsgaard Thomsen, Bolette Hartmann, Yi-Chun Chen, Anna E. Jonsson, Hasan Kabakci, Swaraj Thaman, Niels Grarup, Christian T. Have, Lindsay P. Pallo, Kristine Faerch, Anette P. Gjesing, Sameena Nawaz, Jane Cheeseman, Matthew J. Neville, Oluf Pedersen, Mark Walker, Han Sun, Christopher Jennison, Andrew T. Hattersley, Jens F. Rehfeld, Rury R. Holman, B
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