US researchers scanned the DNA of nearly 28,000 people taking weight loss drugs, which mimic natural hormones that influence appetite and metabolism. (Photo: Freepik)Why do people on the new weight loss drugs, which are being seen as effective tools in managing obesity and diabetes, not working for everyone equally? In fact, some users say the drugs have little to no impact on them compared to others who say they have lost weight significantly. A new study published in Nature says that the efficacy of weight loss drugs may now be dependent on genes. Some, of course, may give up because of severe gastric tolerance issues and side effects like severe nausea.US researchers scanned the DNA of nearly 28,000 people taking weight loss drugs, which mimic natural hormones that influence appetite and metabolism. Semaglutide (sold under brand names Ozempic, Wegovy), for example, mimics a hormone called glucagon-like peptide-1 (GLP-1), while tirzepatide (Mounjaro) mimics both GLP-1 and the hormone glucose-dependent insulinotropic polypeptide (GIP). In one study, participants taking semaglutide lost an average of 10% of their body weight — but some lost more than 25% and others lost almost none.The gene linkResearchers at the non-profit 23andMe Research Institute found that people carrying one copy of a specific variant in the gene that helps the drug bind to the receptor for GLP-1 lost, on average, 0.76 kilograms more over a median of eight months of treatment than did people who had no copies. People carrying two copies of the variant lost around 1.5 kilograms more.Also Read | Beyond the weight-loss injection: How this 44-year-old balances Mounjaro with diet, exercise and sleepThe gene was also associated with the severity of nausea and vomiting in patients on both drugs. Tirzepatide was found to significantly raise the risk of vomiting.What does this mean for Indians?“In the Indian context, emerging evidence suggests that variability in weight loss is partly genetically determined,” says Dr Anoop Misra, Chairman at Fortis CDOC Hospital for Diabetes and Allied Sciences, New Delhi. “Our earlier work in Indian populations demonstrated that variants in genes such as FTO and VDR significantly influence response to dietary interventions. It was also observed that some genes (e.g. Neurobeachin gene, reported in 2025) may modulate weight loss trajectories in individuals receiving GLP-1–based therapies. The present study strengthens this evidence with more robust data,” he adds.He sees these findings as particularly relevant for India, given the heterogeneity in obesity phenotypes and the growing use of GLP-1 drugs. “Going forward, well-designed studies in Indian populations are needed to determine whether genetic profiling can help personalise obesity treatment and identify individuals most likely to benefit from specific weight-loss therapies,” he says.Varying responses among Indians tooDr V Mohan, Chairman, Dr Mohan’s Diabetes Specialities Centre, Chennai, has been observing differential responses in his patients, who were on the earlier versions of GLP1s like liraglutide. “I have seen four types of response among Indians. The best response was when both HbA1c (average blood sugar count of three months) and weight were reduced. One group reported better weight loss, another reported only a dip in HbA1c. And in a stubborn fourth group, neither weight nor HbA1c came down. I called them super, partial and non-responders to these groups of drugs. Luckily the last is a small number,” he says.Story continues below this adMust Read | Quitting weight-loss jabs like Ozempic and Mounjaro leads to rapid weight regain in 1.5 years, says new BMJ studyDr Mohan has been working on the gene connection. “This is what we call pharmacogenomics or the study of how an individual’s genetic makeup affects their body’s response to drugs. By analysing DNA, this field helps healthcare providers select the best medications and dosage to maximise efficacy and minimise adverse side effects,” says Dr Mohan.Although this research is the first to show the gene connection, he feels many more could show how drug efficacy varies between ethnicity, gender, age and even the sub-group of Type 2 diabetes. “For example, those with Insulin Resistant Obese Diabetes (IROD) — which is characterized by a combination of high body mass index (BMI), high waist circumference and high insulin resistance, may respond well to weight loss drugs. Patients in this group produce insulin but their bodies cannot use it effectively due to obesity-related resistance. However, those with insulin-deficient Type 2 diabetes may not respond as well,” explains Dr Mohan.He even talks about another class of drugs, which work by preventing the breakdown of the body’s own gut hormones rather than mimicking them. “These are known to be significantly more effective in Indians and Koreans than in other ethnic groups. This study is on Caucasians. We need more studies to judge the efficacy of drugs on South Asians, which include Indians,” he says.Rinku Ghosh is the Health Section Lead at The Indian Express, where she oversees the publication’s comprehensive health, wellness, and medical science vertical. With years of experience in high-impact journalism, Rinku specializes in translating complex medical research into actionable insights for the public. Her reporting spans a wide spectrum—from deep-dives into childhood obesity and the effects of urban pollution to the frontiers of medical technology, such as the use of AI and nanobots in cancer treatment. Authoritativeness: As a veteran editor at one of India’s most trusted news organizations, Rinku has interviewed world-renowned experts, including cardiologists from the Mayo Clinic, oncologists from AIIMS, and researchers from the Indian Institute of Science (IISc). Her column often serves as a primary source for "Explained" features, where she breaks down global health trends, vaccine safety, and public health policy. Her work is recognized for bridging the gap between clinical data and the lived experiences of patients. Trustworthiness: Rinku’s editorial approach is rooted in the "Journalism of Courage" philosophy, prioritizing evidence-based science over healthcare myths. In an era of medical misinformation, she ensures that every piece of advice—whether regarding chronic disease management or nutritional supplements—is backed by peer-reviewed studies and verified by leading medical practitioners. ... Read More © IE Online Media Services Pvt Ltd