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Some people taking the new generation of obesity drugs lose one-quarter of their body weight.Credit: Peter Dazeley\/Getty<\/p>\n
Most people taking the popular <\/a>GLP-1 drugs<\/a> shed substantial amounts of weight \u2014 an average of one-quarter of their body weight according to one study1<\/a>. So why do 10\u201315% of people using the drugs lose minimal weight or none at all?<\/p>\n \u201cThere is tremendous heterogeneity\u201d in the response to these medications, says Daniel Drucker<\/a>, an endocrinologist at the University of Toronto in Canada, whose work aided in the development of GLP-1 drugs. \u201cAnd we really don\u2019t understand that.\u201d<\/p>\n Why do obesity drugs seem to treat so many other ailments?<\/p>\n <\/a><\/p>\n Solving this mystery might lead to new medications<\/a> for people who do not benefit from today\u2019s versions of such drugs, and could make it possible to match individuals to treatments that are most likely to work for them. Those tantalizing possibilities have made people\u2019s individualized responses to GLP-1s a key line of enquiry for obesity scientists. The Endocrine Society, a leading medical and research organization in Washington DC, has already called for it to be a priority for the field, with scientists looking into various explanations, including biological sex, genetics and behavioural factors.<\/p>\n For now, research to identify the differences between those who do or don\u2019t respond to the drugs is in its early days, and precision medicine for obesity remains \u201clargely aspirational\u201d, according to a scientific statement published by the Endocrine Society<\/a> earlier this month. But researchers are starting to dig into these questions with energy.<\/p>\n Oestrogen effect<\/p>\n One factor that has already been the subject of study is the link between biological sex and response to GLP-1 drugs. Clinical trials2<\/a> and real-world data3<\/a> consistently show that women tend to lose more weight than do men on the medications, which mimic a natural hormone called glucagon-like peptide 1 and are prescribed for obesity and type 2 diabetes<\/a>.<\/p>\n How to keep weight off after obesity drugs<\/p>\n <\/a><\/p>\n In a 2024 study4<\/a> of postmenopausal women who were taking the GLP-1 drug semaglutide, those who also received hormone-replacement therapy<\/a> lost more weight than those who did not have the hormone therapy. A study5<\/a> published in February found similar results for women who took tirzepatide, a drug that mimics both GLP-1 and a hormone called gastric inhibitory polypeptide.<\/p>\n This suggests that oestrogen, a female sex hormone that is given as part of hormone-replacement therapy, might enhance the effects of the obesity drugs, says Drucker. \u201cWe don\u2019t yet understand the molecular mechanism. But I have confidence we\u2019ll be able to make headway there,\u201d he adds. Animal studies6<\/a> have already shown that oestrogen reduces food intake and acts on similar brain regions to GLP-1. Research has also highlighted that combining GLP-1 and oestrogen has a synergistic effect on weight loss.<\/p>\n Genetic influence<\/p>\n Scientists are only just beginning to understand how genes might affect people\u2019s response to obesity drugs, says Ruth Loos, a genetic epidemiologist at the University of Copenhagen. \u201cWe know a lot about the genetics of obesity,\u201d she says, \u201cbut when it comes to the genetic contribution to the response to weight-loss drugs \u2026 there\u2019s not a lot of good data available.\u201d<\/p>\n![\"\"](\"https:\/\/www.newsbeep.com\/uk\/wp-content\/uploads\/2026\/09\/d41586-026-03020-3_27707328.jpg\"\/)
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