Kentucky Trial Tests Whether Semaglutide Can Reverse Heart Damage From Childhood Obesity

Researchers at the University of Kentucky are leading a clinical trial to determine whether the drug semaglutide can reverse early signs of heart disease in children with severe obesity, a condition with long-term health consequences in a state with one of the highest childhood obesity rates in the US.

The trial, called the MODERN study (Mitigation of Cardiovascular Disease Risks in Pediatric Extreme Obesity), is led by John Bauer and Aurelia Radulescu of the UK College of Medicine, and examines how semaglutide, a GLP-1 receptor agonist sold as Ozempic and Wegovy, affects the cardiometabolic risk of adolescents. The clinic Radulescu founded in 2008 receives as many as 1,000 new patient referrals a year and now has more than 140 patients on pharmacological weight-loss treatment.

Semaglutide has been approved by the FDA for children ages 12 to 18 since 2022, but long-term data in that age group remain limited. Radulescu said the medication should be prescribed only when clinically necessary, not for cosmetic reasons, and that the clinic screens out patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 before prescribing, alongside low-dose use and monthly monitoring.

Early rodent studies found an increased risk of medullary thyroid carcinoma linked to GLP-1 drugs, but healthy human thyroid cells contain almost no GLP-1 receptors, which may explain why the mechanism seen in mice has not been replicated in humans. Some human observational studies have suggested a possible elevated thyroid cancer risk, while other large studies have found no association. Longer-term adult trials have largely dispelled earlier concerns about acute pancreatitis or pancreatic cancer.

Children with severe obesity often show thicker heart walls, larger chambers and increased left ventricular mass compared with healthy-weight peers, raising their risk of major cardiovascular problems in adulthood. Bauer said the known risks of untreated childhood obesity must be weighed against the very low incidence of serious side effects.