Genetic variations may help explain why some patients respond better than others to widely used weight-loss medications, according to new research that points to the potential for more personalised treatment approaches.
Drugs such as Ozempic, Mounjaro and Zepbound have transformed the treatment of obesity in recent years. These medications belong to a class known as GLP-1 receptor agonists, which mimic a natural hormone that regulates appetite and blood sugar, helping people feel full for longer. Despite their growing use, patient outcomes vary widely, with some individuals losing less than 5 percent of their body weight while others achieve reductions exceeding 20 percent.
The study, conducted by researchers at the 23andMe Research Institute and published in Nature, examined genetic data alongside patient-reported experiences to better understand these differences.
Researchers analysed information from nearly 28,000 participants who had taken GLP-1 medications for a median period of just over eight months. Their findings identified specific genetic variants that appear to influence how individuals respond to these treatments.
One such variation in the GLP1R gene was linked to improved effectiveness. Individuals carrying a particular version of this gene lost an average of 0.76 kilograms more than those without it during the study period. Another variant in the GIPR gene was associated with an increased likelihood of side effects such as nausea and vomiting among patients taking tirzepatide-based drugs, though it did not affect weight loss outcomes.
Noura Abul-Husn, chief medical officer at the research institute, said current approaches to weight management often rely on trial and error. She noted that patients frequently begin treatment without clear expectations about how effective a drug will be or what side effects they might experience.
Experts not involved in the study said the findings offer useful insight but should be interpreted with caution. Marie Spreckley of the University of Cambridge said the genetic effects identified are relatively small in clinical terms, especially compared with the typical weight loss of 10 to 15 percent seen in trials of these medications. She added that factors such as dosage, treatment duration, sex and drug type likely play a larger role in determining outcomes.
Still, researchers believe the results could mark a step toward more tailored therapies. Cristóbal Morales, a specialist in metabolic health in Spain, said the ability to predict how patients will respond to treatment through pharmacogenomics could improve both drug selection and safety.
The findings highlight the growing interest in personalised medicine, where treatments are adapted to an individual’s genetic profile, though further studies are needed to confirm how these insights can be applied in clinical practice.
