July 24, 2025, 12:05 pm | Read time: 5 minutes
Ozempic, Wegovy, and similar medications are gaining popularity for their effectiveness in weight loss. These drugs, originally developed to treat diabetes, are now being used off-label for weight management. The active ingredient, semaglutide, works by mimicking a hormone that regulates appetite, leading to reduced food intake. As demand increases, experts are raising concerns about potential side effects and the ethical implications of using these medications for non-diabetic purposes. The effect of the so-called weight loss injections can vary from user to user for various reasons. In a study, researchers have now demonstrated a strong influence of certain gene variants on the effectiveness of Ozempic, Wegovy, and others. FITBOOK takes a closer look.
Why Weight Loss Injections Don’t Work for Everyone
Originally developed for the treatment of diabetes, “weight loss injections,” whose active ingredients are often available in tablet form, have been used for treating obesity since 2022. Their mechanism is known: Simply put, these GLP-1 agonists increase the feeling of fullness and curb appetite. As a result, users feel the need to eat less and lose weight. However, this is not universally true. Some people do not experience the expected effects from weight loss injections. This can have various causes. According to a new study, certain gene variants are crucial in this context.1
The study focused specifically on the role of Neurobeachin (NBEA). This gene is known to produce a specific protein that plays an important role in signal processing in the brain, affecting appetite and the feeling of fullness. Previous studies had already suggested that NBEA can influence eating behavior, body weight, and the sense of reward. The research team wanted to investigate more closely how NBEA might affect the effectiveness of weight loss injections in certain individuals.
Details of the Study
The researchers analyzed health data from about 6,500 individuals from the large U.S. “All of Us” study. These individuals had received treatment with the GLP-1 receptor agonists liraglutide or semaglutide. Importantly, the scientists found about 2,800 different gene variants in the NBEA gene, which are minimal changes in individual “letters” of the genetic code. Some of these variants were particularly common in people who had lost significant weight through the weight loss injections. The researchers defined these as “responsive” gene variants. In contrast, the “non-responsive” variants were predominantly found in individuals who had little or no weight loss under GLP-1 therapy.
Based on this data, the researchers developed a so-called “NBEA gene score.” This score is intended to predict, based on genetic characteristics, how likely it is that a person will lose significant weight through treatment with a GLP-1 medication. To verify this score, 241 participants from the UK Biobank long-term study served as an independent control group.
Using the statistical method of logistic regression, the researchers assessed how the gene score correlated with actual weight loss. They specifically looked at whether someone was among the 20 percent of participants who had lost a significant amount of weight or among those for whom the weight loss injections did not seem to work, as they had not lost any weight.
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Results and Their Possible Significance
The analysis showed that participants with a “responsive” gene variant—or more precisely, a favorable gene score combination—had up to an 82 percent higher likelihood that the weight loss injections would be effective for them. For individuals with a “non-responsive” NBEA variant, the chance of responding to treatment with semaglutide or liraglutide was only about 50 percent.
“The results suggest that genetic variations in the NBEA gene can predict weight loss under treatment with GLP-1 receptor agonists,” the study authors write. This could have significant practical implications. The so-called weight loss injections can have unpleasant and sometimes serious side effects.2 These range from gastrointestinal issues like nausea and constipation to pancreatitis.3 Being able to assess before starting a potential therapy whether the medication will be effective for a person could help avoid unnecessary treatments (with possible side effects).
Limitations
The authors point out various limitations. No dedicated clinical study was conducted; instead, the researchers based their investigation solely on electronic health records. This can introduce confounding factors—there was, for example, no way to verify medication adherence. Additionally, there were differences in the active ingredients used. Liraglutide was often administered in the classic diabetes dose, not in the higher dose typically used for targeted obesity treatment. Overall, the authors suggest that individual GLP-1 agonists may need to be considered differently.
The study exclusively examined gene variants. It should be noted that various factors can influence the effectiveness of weight loss injections, starting with the consistency of treatment and dosage. It is also suspected that stress and individual predispositions can affect the efficacy of semaglutide and others. Experts particularly emphasize that these medications are just one component among many on the path to a healthy body weight. “Lifestyle change is key,” a university researcher told FITBOOK regarding GLP-1 therapies. This includes incorporating exercise and maintaining a healthier diet. It is also clear that if users eat less overall due to the appetite-suppressing effect but consume high-calorie and “unhealthy” snacks, the desired weight loss will not occur.