Drug for obese adults also works for teens, study says

An injectable drug already approved in the United States for obese and overweight adults, semaglutide (wegovy) also helps teenagers lose weight and reduce cardiovascular risk.

This is what a study published this Wednesday (2) in the New England Journal of Medicine and presented at Obesity Week, the largest international conference on obesity that takes place in San Diego, California (USA) shows.

In the multicenter phase 3 clinical trial, obese adolescents who received the substance once a week had a 16.1% reduction in their BMI (body mass index), which is the division of weight by height squared. In the group that took a placebo, the rate increased by 0.6%.

On average, participants using semaglutide lost 15.3 kg, while those on placebo gained 2.4 kg over a 68-week period.

The study included 201 adolescents aged between 12 and 18 years, with an average weight of 107.5 kg and a BMI of 37 kg/m2, on average.

When the result is between 25 and 30, overweight is considered — a condition that affects 57% of the adult population in Brazil, according to Vigitel (Surveillance of Risk and Protection Factors for Chronic Diseases by Telephone Survey). If the BMI is greater than 30, the case is categorized as obesity, which currently affects 22% of the adult Brazilian population.

Study participants received subcutaneous injections of semaglutide 2.4 mg or placebo. They were also instructed on healthy nutrition and physical activity. The study was funded by Novo Nordisk, the drug’s maker.

“Until now, we had few alternatives to treat obese adolescents. This weight loss [mostrada no estudo] never been seen in this age group. We were all very impressed,” says Cíntia Cecato, an endocrinologist at the Hospital das Clínicas in São Paulo, who chairs Abeso (Brazilian Association for the Study of Obesity and Metabolic Syndrome).

Endocrinologist Bruno Halpern, who assumes the presidency of Abeso in January, also celebrated the results of the study, but reinforces that they do not reduce the importance of maintaining a focus on improving the quality of food and exercise. “On the contrary, joining strategies is always better. These encouraging results can even increase adherence to these strategies [não medicamentosas] in that age group.”

Semaglutide, originally prescribed for diabetes, is awaiting approval from Anvisa (National Health Surveillance Agency) for the treatment of obesity in adults, but it has been widely used in the country off-label (when a drug is prescribed for a purpose different from that seen in the leaflet). Novo Nordisk states that it “does not endorse or support the promotion of off-label information”.

The substance mimics a hormone naturally produced by the intestine, GLP-1, which, among other functions, reduces appetite and slows digestion, which makes a person eat less food.

“The degree of reduction in body weight is unprecedented. After years of frustration, suddenly patients really started to lose weight,” said Daniel Weghuber, from Paracelsus Medical University, Salzburg (Austria), lead author of the study.

The only obesity treatment approved for adolescents in Brazil is liraglutide (saxenda), which was approved by Anvisa in 2020. The new study suggests that semaglutide outweighs the benefits of this substance and others that have already been approved for adolescents in the US, such as orlistat and phentermine-topiramate.

According to the study, other indicators of cardiovascular risk improved in the semaglutide group compared to the placebo group, including high cholesterol (-8.3 versus -1.3), triglycerides (-28.4 versus 2.6 ) and alanine transaminase levels (-18.3 versus -4.9).

Weghuber points out that with semaglutide, there were also improvements in weight-related quality of life, which was not seen in previous trials with other drugs.

He said the weight loss observed in the study was greater in adolescents than in adults taking semaglutide. It is unclear why this happened.

Participants who took semaglutide were more likely to have gastrointestinal side effects such as nausea compared with the placebo group (62% versus 42%), which is also true among adults. But, in general, they were well tolerated and with no new safety concerns.

The results come at a time when obesity and overweight rates are on the rise around the world.

A recent Harvard University study projected that by 2030 nearly half of Americans will be obese, which will account for up to 18% of healthcare spending to treat obesity-related conditions such as heart disease, stroke and osteoarthritis.

According to the 2020 National Health Survey, among teens aged 15 to 17, 1 in 5 were overweight (19.4%) and 6.7% were obese. Another study with adolescents followed up in primary care in 2021 showed that 32.7% and 13% were overweight and obese, respectively.

Among children up to 5 years old, 15.8% were overweight. Between 5 and 9 years old, the rate was 33.9% of children. Of these, 7.6% and 17.8%, respectively, were obese.

“Lifestyle recommendations like eating more vegetables, not eating fried foods, not drinking soda are still valid, but it is very difficult for people to make these changes. There is a real need for safe and effective drugs to treat obesity,” said Nikhil. Dhurandhar, professor of nutritional science at the University of Texas (USA).

For cardiologist and specialist in evidence-based medicine Luís Correia, professor at the Bahia School of Medicine and Public Health, there is good-quality evidence that these new drugs, compared to placebo, significantly reduce a person’s weight. “In addition to being more effective than the old anorectics, they do not cause the side effects [que eles causavam]. They represent a real pharmacological evolution.”

In his opinion, however, it is a mistake to think that obesity is an individual clinical problem and that it is enough to treat it with medication. “It’s a population problem. Note that there are people, like the Japanese, whose culture is different, and obesity is 3%, against 30% in Brazil. It’s not genetics, it’s behavior.”

There are no objective data on the durability of the effect of semaglutide among adolescents, but studies in adults show that weight loss was maintained for two years of continuous treatment. Another study, however, shows that adults who lost weight regained about two-thirds of it during the first year after stopping the medication.

The maintenance of long-term weight loss is another challenge and requires public prevention policies. “People live in an obesogenic environment, with ultra-processed foods, an increasingly sedentary lifestyle”, says Cíntia Cecato, from Abeso.

Among the preventive measures suggested by the WHO (World Health Organization) are the higher taxation of sugary drinks, the ban on advertising of ultra-processed foods aimed at children and the creation of safe urban spaces where people can exercise.

The journalist traveled at the invitation of Novo Nordisk