GLP-1 drugs fail 10-15% of users; scientists probe sex, genetics for answers

September 25, 2026 at 02:01 AM2 min

This digest was compiled by AI from multiple sources — links to the originals are below.

A subset of 10–15% of people taking GLP-1 obesity drugs lose minimal or no weight, despite an average loss of one-quarter of body weight in most users. Researchers are investigating biological sex, genetics, and behavioural factors to explain this variability. The Endocrine Society has called precision medicine for obesity a priority, though it remains largely aspirational.

Key Facts

10–15% of people taking GLP-1 drugs lose minimal weight or none at all, according to Nature News.
Most people taking GLP-1 drugs shed an average of one-quarter of their body weight, based on one study.
Clinical trials and real-world data consistently show that women tend to lose more weight than men on GLP-1 medications.
In a 2024 study of postmenopausal women on semaglutide, those who also received hormone-replacement therapy lost more weight than those who did not.
A study published in February found similar results for women who took tirzepatide, a drug that mimics both GLP-1 and gastric inhibitory polypeptide.

Response Variability

Daniel Drucker, an endocrinologist at the University of Toronto whose work aided in the development of GLP-1 drugs, says there is tremendous heterogeneity in response to these medications. He adds that researchers really do not understand why some people see minimal benefit. The Endocrine Society, a leading medical and research organization in Washington DC, has called for individualized responses to GLP-1s to be a priority for the field. A scientific statement published by the Endocrine Society earlier this month describes precision medicine for obesity as largely aspirational.

Sex Differences

Clinical trials and real-world data consistently show that women tend to lose more weight than men on GLP-1 medications, which mimic a natural hormone called glucagon-like peptide 1. In a 2024 study of postmenopausal women taking semaglutide, those who also received hormone-replacement therapy lost more weight than those who did not. A study published in February found similar results for women who took tirzepatide, a drug that mimics both GLP-1 and another hormone called gastric inhibitory polypeptide. Drucker suggests that oestrogen, a female sex hormone given as part of hormone-replacement therapy, might enhance the effects of the obesity drugs. He says the molecular mechanism is not yet understood, but he has confidence researchers will be able to make headway there.