GLP-1 receptor agonists (RAs) improve blood glucose control and reduce weight in children and teens with diabetes or obesity, according to a new study published online in JAMA Pediatrics.

Children taking the drugs also did not exhibit differences in depression or suicidal behaviors compared with those taking a placebo, despite GLP-1 RA labels containing a warning of suicidal behavior and ideation.

“The findings could give clinicians confidence in prescribing these medications, as they support the current American Academy of Pediatrics guideline on their use in pediatric patients,” said Jingchuan Guo, MD, PhD, assistant professor in the Department of Pharmaceutical Outcomes and Policy at the University of Florida in Gainesville, Florida, and coauthor of the study.

The FDA has approved two GLP-1 RAs for weight management in adolescents aged 12 years or older with obesity: liraglutide (Saxenda) in December 2020 and semaglutide (Wegovy) in December 2022. In 2023, the American Academy of Pediatrics said pediatricians should offer weight loss pharmacotherapy to children aged 12 years or older with obesity as an adjunct to health behavior and lifestyle treatment. 

The new meta-analysis analyzed data from 18 randomized controlled trials comparing GLP-1 RAs with placebo in 1402 participants between the ages of 6 and 17 years. The participants in the trials were followed up to 1 year. The drugs included exenatide, liraglutide, semaglutide, dulaglutide, and lixisenatide.

Compared with placebo, GLP-1 RAs significantly reduced A1c (-0.44% of absolute A1c; 95% CI, -0.68% to -0.21%), body weight (-3.02 kg; 95% CI, -4.98 to -1.06), BMI (-1.45; 95% CI, -2.40 to -0.49), and systolic blood pressure (-2.73 mm Hg; 95% CI, -4.04 to -1.43). The medications were also associated with a decreased rate of suicidal ideation or behaviors (log rate ratio, -0.46; 95% CI, -1.42 to 0.49), although this outcome was not statistically significant. 

While the study showed efficacy, Guo said the sample size was too small to make any conclusions about safety. 

“We still need real-world data to see how these medications work in this vulnerable population,” Guo told Medscape Medical News. A larger sample size and a longer observation period are necessary to find out “whether these medications are going to have a long-term impact on the development and growth of these children and adolescents.” 

The study also found the therapies showed a trend toward increased rates of hypoglycemia across seven trials (log rate ratio, 0.51; 95% CI, -0.07 to 1.08), but the effect was not statistically significant. Guo said this finding is not commonly reported in the adult population. 

Rise in Pediatric Prescriptions

Approximately 1 in 5 children and adolescents have obesity, which increases the risk for type 2 diabetes, according to the CDC.

The American Diabetes Association recommends that physicians consider GLP-1 RAs in children aged 10 years or older if glycemic goals are no longer met with metformin, with or without long-acting insulin.

The proportion of US adolescents prescribed obesity medications increased by approximately 300% in 2023 compared with 2020, as reported in the CDC’s Morbidity and Mortality Weekly Report in June. Despite the spike, less than 1% of adolescents with obesity were prescribed one of the drugs, including orlistat, liraglutide, or semaglutide. A majority of prescriptions (83%) were for adolescents with severe obesity.

Joyce Lee, MD, MPH, professor of pediatrics and communicable diseases at the University of Michigan Medical School in Ann Arbor, Michigan, and coauthor of the JAMA study, said the biggest barriers to GLP-1 RA dispensing are coverage by insurers and the comfort of pediatricians in prescribing the medications, despite interest by families and patients. 

“I think the consumer demand itself is probably a bigger conversation focus on childhood obesity now with our pediatricians, and I would say that the exuberance with which [pediatricians] willing to collaborate with endocrinologists on this is actually really being driven by the fact that they have families coming to them saying, ‘Hey, I want this medication,’” Lee said.

Evaluations of Suicidal Risks

Guo said the new findings support the use of GLP-1s in pediatric patients, but that more research is needed on associations with mental health outcomes.

The Saxenda label states that in a pediatric clinical trial, one (0.8%) of the 125 patients died by suicide, but researchers could not establish a causal relationship with the drug because of insufficient information. 

The FDA later reviewed reports submitted to its Adverse Events Reporting System and, in 2024, said that it did not find evidence that the use of these medicines caused suicidal thoughts or actions. 

“However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, we cannot definitively rule out that a small risk may exist; therefore, the FDA is continuing to look into this issue,” the agency said in a drug safety communication at the time.

Another study published at that same time found that semaglutide was associated with a lower risk for incident and recurrent suicidal ideation than those who took non-GLP-1 obesity drugs. Another study published in JAMA Pediatrics later that year found adolescents with obesity who received GLP-1 RA treatment had a 33% lower risk for suicidal ideation or attempts at up to 3 years of follow-up than the control group who initiated behavioral interventions. 

Guo reported having no financial conflicts of interest. Lee reported receiving a grant from Eli Lilly and Company for a quality improvement project. 

Brenda Sandburg is a freelance journalist who has written about the biopharmaceutical industry and legal issues for The Pink Sheet and The American Lawyer.