New Delhi: A new study has found that three popular obesity drugs reduced body weight in mice with early-onset obesity. The findings suggest that medicines based on the GLP-1 hormone may work even in rare forms of obesity caused purely by genetic defects.
GLP-1 drugs are medicines that copy a natural gut hormone which is released after eating and signals to the brain that the body is full.
The study shows it may work on those with genetic obesity that starts at birth.
The research, published in the International Journal of Obesity on 21 February 2026, tested semaglutide, tirzepatide and retatrutide in mice that lack the Melanocortin 4 receptor, also known as MC4R. MC4R is a receptor in the brain, which receives signals to balance hunger and energy. When this receptor does not function properly because of a genetic mutation, a person can develop severe obesity from early childhood. Doctors say such cases are rare and treatment options for such rare genetic obesity are limited.
While semaglutide is the obesity drug developed by Danish drugmaker Novo Nordisk and sold under brand names Ozempic, Wegovy and Rybelsus, tirzepatide and retatrutide is developed by the US based pharmaceutical company Eli Lily.
GLP-1 also slows down stomach emptying, which means food stays in the stomach longer, and increases insulin release, which helps lower blood sugar levels. Because they reduce appetite and improve blood sugar control at the same time, these medicines are used to treat both type 2 diabetes and obesity.
Among the obesity drugs which mimic the natural hormone GLP-1, semaglutide works by activating only the GLP-1 receptor, helping people feel full sooner and eat less.
Tirzepatide acts on two hormones—GLP-1 and GIP, which is another gut hormone involved in blood sugar regulation—and this dual action may lead to greater weight loss.
Retatrutide, which is still under development, targets three hormones—GLP-1, GIP and glucagon, which is a hormone involved in energy balance—and is designed to have a broader effect on metabolism.
Semaglutide and tirzepatide are already available in India, while retatrutide is expected to enter the market in the future.
How scientists tested GLP-1 drugs for rare genetic obesity
In the study, researchers used specially bred laboratory mice that do not have a working MC4R gene. Because this gene normally controls appetite, these mice develop hyperphagia, a medical condition where the person has insatiable hunger accompanied by abnormal food seeking behaviours.
As a result, they become severely obese at an early age. The mice also showed insulin resistance, which means their bodies are unable to break down sugar into energy.
They had high cholesterol and triglycerides, which are fats in the blood, and elevated liver enzymes such as AST and ALT, which are markers that can indicate liver stress.
The mice were given daily injections of one of the three drugs (semaglutide, tirzepatide and retatrutide) for 21 days. After three weeks, all three drugs reduced body weight. Mice given semaglutide lost about 19.7 per cent of their weight; those given tirzepatide lost 31.6 per cent; mice given retatrutide lost 24.1 per cent.
The study was conducted by Japanese researchers Kosuke Hitaka, Takumi Sugawara, Mitsuharu Matsumoto and Yasunori Nio. The authors explained that most obesity drugs are first tested in diet-induced obesity models, in which mice are fed a high-fat diet for more than six months until they become obese. This makes research slow and delays drug development. In contrast, MC4R-deficient mice develop severe obesity at a young age because of their genetic defect, which allows faster testing of anti-obesity medicines.
The researchers said the magnitude and pattern of weight loss seen in these mice were highly consistent with results reported in human clinical trials of GLP-1 drugs. They also observed loss of lean body mass, similar to what has been reported in people taking these medicines.
‘Uncommon condition’
Commenting on the findings, Chennai-based diabetologist Dr V. Mohan, an obesity researcher and the chairman of the Madras Diabetes Research Foundation (MDRF), said, “These kinds of genetic forms of obesity are what are called monogenic forms of obesity. They are extremely rare in humans.”
“I myself may have seen only one or two such cases in my lifetime,” he added.
He cautioned that results in mice may not always directly apply to people.
Dr Mohan explained that in rare instances, children with certain genetic defects affecting hunger control can become severely obese from the age of one or two, and this is not due to overeating but due to a biological problem in appetite regulation.
However, he stressed that most obesity cases are linked to lifestyle factors, hormonal changes or shared family habits rather than a single faulty gene.
Dr Rajiv Kovil, Head of Diabetology at Zandra Healthcare in Mumbai, said that treatment for rare genetic obesity has usually focused on fixing the MC4R pathway, which is a key hunger control system in the brain.
He gave the example of Imcivree, a prescription medication for chronic weight management in patients aged 2 years and older with obesity caused by Bardet-Biedl syndrome (BBS) and other such rare genetic deficiencies. It was approved by the U.S. Food and Drug Administration in 2020. He explained that this medicine works by directly targeting the brain’s appetite switch.
“What is exciting,” Dr Kovil said, “is that newer GLP-1 medicines like semaglutide and tirzepatide seem to still cause meaningful weight loss even when this appetite switch is not working normally.”
(Edited by Viny Mishra)
Also read: Weight-loss drugs are changing. Here’s what to know about GLP-1s