Young adults with severe obesity who remained resistant to hospital-based obesity treatment during childhood experienced clinically significant reductions in body mass index (BMI) and improvements in cardiometabolic health with semaglutide treatment, according to findings from the RESETTLE randomized controlled trial presented at the European Congress on Obesity 2026. The study highlighted the importance of identifying children early who remain resistant to non-pharmacological obesity care and may benefit from the timely addition of glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy.
The placebo-controlled, double-blind trial was conducted in young adults aged 18-28 years who continued to live with severe obesity despite at least one year of treatment at the Children’s Obesity Clinic, European Centre for Obesity Management at Holbæk Hospital. The authors noted that although hospital-based obesity care can reduce childhood obesity, “one in four children are more difficult to treat and a reduced degree of obesity is hard to maintain,” highlighting the need for additional effective and safe treatment strategies.
A total of 246 participants from the HOLBAEK Study were categorized according to prior response to childhood obesity treatment and current BMI status. Joachim Holt and colleagues evaluated whether semaglutide could improve obesity severity and cardiometabolic health in participants with low or medium response to earlier obesity care.
The analysis included 162 participants in the low- and medium-response groups who continued to live with obesity as young adults. Participants were randomly assigned to once-weekly semaglutide 2.4 mg or placebo for 68 weeks. Baseline assessments included waist circumference, lipid profile, blood glucose, blood pressure, dual-energy x-ray absorptiometry body composition imaging, and magnetic resonance imaging evaluation of liver and visceral fat. Overall trial retention was high, with 94% of participants attending the final study visit.
After 68 weeks, semaglutide treatment led to an average BMI reduction of 19% and average weight loss of 22.3 kg in both the low- and medium-response groups compared with placebo. In the low-response group, BMI decreased by 7.3 kg/m² from a baseline of 40.5 kg/m² with semaglutide, whereas BMI increased by 0.5 kg/m² with placebo. Similarly, in the medium-response group, BMI decreased by 6.7 kg/m² from a baseline of 38.0 kg/m² with semaglutide but increased by 0.6 kg/m² with placebo.
Semaglutide treatment was also associated with marked reductions in total fat mass, abdominal fat, and liver fat compared with placebo. In the low-response group, total fat mass decreased by 17 kg and abdominal fat by 48%, while corresponding reductions in the medium-response group reached 15 kg and 41%, respectively. Liver fat decreased by 39% and 34% in the low- and medium-response groups. Metabolic syndrome severity scores also improved substantially, with reductions of −0.80 and −0.58, respectively, reflecting improvement across lipids, blood pressure, fasting glucose, and waist circumference.
Semaglutide was safe and generally well-tolerated. The most commonly reported adverse events were gastrointestinal symptoms, including nausea and abdominal pain. The authors noted that side effects were generally manageable, improved over time, and did not lead to excess participant withdrawal.
“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.
Study lead Signe Sørensen Torekov stated that “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,” She added that supporting families to implement increased physical activity and healthy behaviors “should remain the foundation of all treatments for childhood obesity and prevention of obesity across generations.”
Jens-Christian Holm added that “childhood obesity is a chronic disease resulting in numerous complications reducing physical, mental, and social thriving during growth and development,” and stated that optimizing obesity treatment with pharmacotherapy in selected patients “is a worldwide imperative.”
