ECO 2026
Childhood obesity care nonresponders lose weight on semaglutide
Clinical Takeaway: Prior non-response to structured pediatric obesity care does not predict non-response to GLP-1 therapy. Identifying treatment-resistant patients earlier, rather than after years of failed lifestyle care, may shorten the window in which cardiometabolic damage accumulates.
A persistent question in obesity medicine is whether patients whose disease resists one treatment carry a biology that will resist others. The answer matters most for young adults whose obesity began in childhood and persisted through structured care, since they enter adulthood already carrying elevated risks of early-onset type 2 diabetes, cardiovascular disease, fatty liver, and several cancers. The RESETTLE trial, presented at the European Congress on Obesity in Istanbul, tests whether years of unsuccessful lifestyle treatment signal a phenotype that also resists pharmacotherapy.
Semaglutide produced a 19% reduction in BMI versus placebo over 68 weeks, corresponding to an average weight loss of 22.3 kg (49.2 lbs). Low and medium responders to childhood care benefited equally. Cardiometabolic outcomes moved in the same direction.
Total fat mass fell 17.4 kg (38.4 lbs) and 15.1 kg (33.3 lbs) in the low- and medium-response groups versus placebo. Visceral fat dropped 48% and 41%; liver fat fell 39% and 34%. Metabolic syndrome severity scores, which combine lipids, blood pressure, fasting glucose, and waist circumference, fell, which the authors link to meaningful decreases in cardiovascular and diabetes risk.
The 162 randomized participants came from the HOLBAEK Study, a Danish cohort of more than 4,000 children and adolescents followed since childhood. All had spent at least a year in pediatric obesity care at Holbæk Hospital's Children's Obesity Clinic and still had a BMI of at least 30 kg/m² as young adults. Participants were randomized 2:1 to weekly semaglutide 2.4 mg or placebo for 68 weeks; 152 (94%) completed the trial. Mean age was 23, and 59% were female.
"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 lead author Joachim Holt, MD, PhD fellow in the Department of Biomedical Sciences at the University of Copenhagen.
Senior author Signe Sørensen Torekov, PhD, professor in the Department of Biomedical Sciences at the University of Copenhagen, added that "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," while noting that family-based support for physical activity and health behaviors should remain foundational across childhood obesity care.
Source: Holt J. Abstract 0688, European Congress on Obesity 2026, Istanbul. Reversing severe persistent childhood-onset obesity: A randomised controlled trial with semaglutide, the RESETTLE Trial