GLP-1 class drugs such as “Ozempic,” “Wegovy,” and “Mounjaro” have radically transformed obesity treatment. According to clinical trials, most users lose 15\u201320% of their body weight. Nevertheless, between 9% and 33% of patients lose less than 5% of their body weight while taking these medications, raising questions about the universal effectiveness of these innovative drugs.<\/p>\n
These patients report being unable to lose weight despite the financial cost of treatment. For some, even switching to alternative versions of the medications does not help. They continue to experience intense food cravings. Even with strict dieting and intensive physical activity, this group achieves only minimal results.<\/p>\n
\u201cGLP-1 resistance means that a specific dose of the drug has a weaker effect on the body, resulting in minimal weight loss and reduced insulin secretion,\u201d explains Mahesh Umapathysivam, a clinical researcher and endocrinologist at the University of Adelaide.<\/p>\n
Scientists attribute the lack of response to several demographic and clinical factors. Researchers have observed that the effectiveness of these medications decreases with age, while men lose significantly less weight than women. A diagnosis of type 2 diabetes also directly affects outcomes \u2014 these patients lose considerably less weight than people without diabetes. Statistics also point to genetic ancestry: the drugs appear to work significantly better in patients of European ancestry.<\/p>\n
Hormonal factors also significantly influence treatment effectiveness, particularly estrogen levels in the body. Research by Australian endocrinologists has shown that phases of the menstrual cycle directly affect the response to GLP-1 drugs. In addition, during menopause, the use of estrogen-containing hormone replacement therapy alongside these medications is associated with faster and more substantial weight loss.<\/p>\n
Another major cause of treatment resistance is thought to be specific genetic mutations. Genetic variants responsible for brain receptors and enzyme production can contribute to pronounced GLP-1 resistance, in which standard doses are no longer able to adequately suppress appetite or slow gastric emptying.<\/p>\n