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Youth with obesity but without type 2 diabetes were 31% less likely to develop type 2 diabetes if they were prescribed a glucagon-like peptide 1 (GLP-1) receptor agonist medication instead of an older-generation obesity medication, according to findings presented at the Pediatric Academic Societies (PAS) 2025 Meeting.

“This study offers compelling early evidence that GLP-1 receptor agonists [GLP-1 RA] may help delay or even prevent the onset of type 2 diabetes in adolescents with obesity — a population at particularly high risk,” Alaina Vidmar, MD, the medical director of the Obesity Medicine and Bariatric Surgery Program at Children’s Hospital Los Angeles, Los Angeles, told Medscape Medical News.

“While the findings are not entirely surprising given what we know about the metabolic benefits of these medications in adults, it’s encouraging to see such a significant risk reduction in a real-world pediatric cohort,” said Vidmar, who was not involved in the study.

Lead investigator Priya Mohan, MD, a third-year pediatric resident at UH Rainbow Babies and Children’s Hospital in Cleveland told attendees that she considers adolescents “a ‘high-alert’ group for chronic diseases, in that they are old enough to develop them but young enough to bear the brunt of disease progression long-term.”

An estimated 20% of US adolescents have obesity, with Black and Hispanic youth disproportionately affected, Mohan said. “This reflects a complex mix of factors, including systemic racism, wealth inequities, political marginalization, and a broken food system,” she said.

Meanwhile, type 2 diabetes in adolescents with obesity is a growing public health concern, she said. “Once considered an adult-onset disease, type 2 diabetes is now increasingly seen in youth, with an incidence of 13.8 per 100,000 per year,” Mohan said. Children with obesity have four times the risk of developing type 2 diabetes as those with a normal body mass index.

“The question remains, when treating obesity in adolescents, what tool is the most useful in this population in not only weight management but also preventing obesity-related complications and sequelae?” Mohan said.

Mohan and colleagues analyzed data from TriNetX, a large, retrospective multicenter and multinational database collected from electronic medical records (EMRs), to identify youth aged 10-19 years with obesity but without type 2 diabetes who were prescribed an obesity medication. They identified 5719 youth who were prescribed any GLP-1 medication, including semaglutide, lixisenatide, albiglutide, liraglutide, exenatide, tirzepatide, or dulaglutide.

They identified 23,700 youth who were prescribed another obesity medication, including bupropion, naltrexone, phentermine, topiramate, orlistat, or metformin.

The researchers then used propensity matching to compare the 5719 patients who received a GLP-1 with 5719 who received an older-generation obesity medication, with no significant differences between the groups in terms of age, gender, race, ethnicity, or average A1c. However, the group who received GLP-1s had an average body mass index (BMI) of 42.2 compared with 40.4 for those receiving another obesity medication (P < .001). The GLP-1 group was also in the 97th percentile for BMI compared with the 96th percentile for the other group (P = .046).

Five years later, 4.3% of those taking GLP-1s had developed type 2 diabetes compared with 6.2% of those who took a non–GLP-1 obesity medication (risk ratio, 0.69; 95% CI, 0.59-0.81).

The study’s limitations included its retrospective design, missing data from the EMR database, and the standard limitations associated with propensity matching.

“These are very exciting findings,” Melanie Cree, MD, PhD, an associate professor of pediatric endocrinology at Children’s Hospital Colorado in Aurora, Colorado, told Medscape Medical News. “Adolescent type 2 diabetes is not the same as adult type 2, and we know from the TODAY study that the development of type 2 diabetes in youth can lead to a much shortened lifespan and comorbidities,” she said.

“We tried in the RISE study to see if metformin or short-term insulin could be used to delay or prevent the onset of type 2 diabetes and they did not. Since all other methods previously tested failed to delay or prevent type 2 diabetes onset, it is great that GLP1-RAs appear to be the first drug category to decrease this risk.” 

The clinical implications of these findings are that GLP-1 medications can decrease the risk for cardiometabolic disease and risk markers in adolescents, Cree said. She was interested in whether a minimal amount of time with GLP-1 treatment was required or whether a certain amount of weight loss was needed to determine which teens are most likely to benefits.

“Our work in teens with PCOS [polycystic ovary syndrome] has shown that oral semaglutide treatment that leads to more than 5% weight loss improves reproductive features of PCOS and MASLD [metabolic dysfunction–associated steatotic liver disease] severity,” Cree said. “In adults, GLP-1 RA use has been shown to improve sleep apnea, MASLD, congestive heart failure, and hypertensive kidney disease, to name a few conditions.”

No external funding was noted, and Mohan had no disclosures. Cree had consulted for Eli Lilly and Novo Nordisk. Vidmar had received consulting fees from Rhythm Pharmaceuticals Inc, Hippo Technologies Inc, and Guidepoint Inc, and grant funding from DexCom Inc.

Tara Haelle is a science/health journalist based in Dallas.