Semaglutide Shows Benefit in Severe, Long-Standing resistant Obesity, finds trial

A weekly dose of semaglutide (2.4 mg) leads to a clinically significant reduction in body mass index (BMI) and related health outcomes in young adults with severe obesity who are treatment resistant following hospital-based non-pharmacological obesity care during childhood, according to a randomised controlled trial being presented at this year’s European Congress on Obesity (ECO) in Istanbul, Turkey (12-15 May).

The study, led by researchers from the University of Copenhagen and Holbæk Hospital in Denmark, underscores the importance of identifying children as early as possible who are resistant to hospital-based obesity care and may benefit from the timely addition of semaglutide or other glucagon-like peptide-1 receptor agonists (GLP-1 RAs).

Semaglutide and other GLP-1 RAs mimic naturally produced incretin hormones, which help to lower blood sugar levels after a meal and decrease appetite causing people to eat less.

Children with obesity are five times as likely to have obesity in adulthood than their healthy-weight counterparts [1]. Obesity that begins in early childhood poses significant health risks in early adulthood, including early-onset type 2 diabetes, cancer, cardiovascular disease, and reduced quality of life.

Hospital-based non-pharmacological obesity care, involving support for children with obesity and their families designed to improve health and thriving during growth and development has been shown to reduce childhood obesity. However, one in four children are more difficult to treat and a reduced degree of obesity is hard to maintain. Therefore, new, effective, and safe treatment strategies are urgently needed.

In the new RESETTLE randomised, placebo-controlled, double-blind trial, researchers investigated the impact of semaglutide treatment in young adults (aged 18-28 years) who were still living with severe obesity despite at least one year of treatment at the Children`s Obesity Clinic, European Centre for Obesity Management at the Holbæk Hospital in Denmark.

The study involved 246 young adults (average age 23 years, 59% female) who were included in the HOLBAEK Study [2] and randomised to four different groups based on their previous response to the paediatric hospital-based treatment programme and their current BMI:

• 82 participants with a low response to childhood obesity care (a change in BMI that was not enough to improve their health) and currently living with obesity as young adults (BMI ≥30 kg/m²).
• 80 participants with a medium response to childhood obesity care and living with obesity as young adults (BMI ≥30 kg/m²).
• 34 participants with a high response to childhood obesity care who did not have obesity as young adults (<30 kg/m²).
• 50 participants from a population-based reference group with normal weight development in childhood.

All participants, regardless of response group, underwent examinations of cardiometabolic biomarkers (waist circumference, lipids in the blood, including cholesterol, blood glucose, and blood pressure), full-body dual-energy x-ray absorptiometry (DXA) images of body composition, and magnetic resonance imaging (MRI) of liver and visceral (abdominal) fat.

The 162 participants in the low- and medium response groups—who had poorer health outcomes compared to the high-response and normal-BMI development groups—were randomly assigned to either weekly injections of semaglutide (2.4 mg; 54 in the low- and 55 in the medium-response group) or placebo (28 and 25) over 68 weeks. In total, 152 (94%) participants attended the final visit.

After 68 weeks, semaglutide led to an average decrease in BMI of 19% (average weight loss 22.3kg) in both the low- and medium-response groups compared with placebo.

In the low-response group, for those taking semaglutide, average BMI decreased 7.3 kg/m² (from 40.5 kg/m²) compared with a minor increase of 0.5 kg/m² in the placebo group. Similarly, in the medium-response group, average BMI decreased 6.7 kg/m² (from 38.0 kg/m²) in those taking semaglutide but increased with 0.6 kg/m² in those who were given placebo (see figure 1 in full abstract).

Participants in the low- and medium-response groups receiving semaglutide also experienced substantial improvements in total fat mass (-17 kg and -15kg, respectively), abdominal fat (-48% and -41%), and liver fat (-39% and -34%) compared to placebo—all key factors in reducing obesity-related health risks. In addition, participants also experienced substantial improvements in the metabolic syndrome severity score (-0.80 and -0.58) which integrates lipids, blood pressure, fasting glucose, and waist circumference into a single value. This reflects a substantial reduction in risk of developing cardiovascular disease and type 2 diabetes.

Semaglutide was safe and generally well tolerated. Gastrointestinal side effects like nausea and abdominal pain were the most common. However, most side effects were manageable, resolved over time, and did not lead to participants dropping out of the trial.

“By reducing the degree of obesity and improving cardiometabolic health irrespective of prior response to childhood obesity care, GLP-1 based treatment could help more young people with severe obesity to reduce their burden of obesity-related complications in early adulthood,” said author Joachim Holt from the University of Copenhagen.

According to study lead Professor Signe Sørensen Torekov at the University of Copenhagen, “Severe obesity in young people is a complex, chronic disease with serious health consequences. GLP-1 based treatment offers a promising option for managing severe obesity in young people who are resistant to prior hospital-based non-pharmacological care. Importantly, supporting families to implement increased physical activity and health behaviours should remain the foundation of all treatments for childhood obesity and prevention of obesity across generations.”

Head consultant, Jens-Christian Holm, the Children`s Obesity Clinic, European Center of Management, Holbæk University Hospital adds that, “Childhood obesity is a chronic disease resulting in numerous complications reducing physical, mental and social thriving during growth and development. Being able to optimise obesity treatment with the addition of drugs in selected patients to improve health is a worldwide imperative.”

Reference:

Semaglutide effective for severe obesity even in young people who have been treatment resistant for many years, finds randomised controlled trial, European Association for the Study of Obesity, Meeting: European Congress on Obesity 2026 (ECO2026)