GPL-1s
Jen Hand
Children and adolescents prescribed GLP-1 receptor agonists for T2D or obesity experienced improvements in several outcomes, according to a study published September 15, 2025, in JAMA Pediatrics. However, the research team cautioned that the adverse GI effects should warrant further scrutiny if considering long-term use.
Nearly one in five children and adolescents in the United States have obesity, with numbers of T2D cases in youth rising in lockstep.
“Diet and lifestyle modification remain the first-line approach for pediatric obesity and type 2 diabetes, and pharmacotherapy is typically considered only when these strategies are insufficient,” said lead author Pareeta Kotecha, PharmD.
Since GLP-1s were first approved for children and adolescents in 2019 by FDA, use of the medications has exponentially increased. Yet Kotecha and colleagues noted critical gaps in existing research, especially for children under age 10 years; non-GI adverse effects; and regulatory concerns, such as suicidal behaviors.
“As use of these medications has increased in younger populations, there is a growing need for evidence on both benefits and potential risks synthesized from existing clinical trials to inform patients, families, clinicians, and regulators,” said Kotecha.
Methods and results
Findings revealed that treatment with GLP-1s significantly reduced weight- related outcomes, including body weight, BMI, BMI standard deviation score (SDS), and BMI percentile. A1C, fasting glucose, and systolic BP numbers also dropped meaningfully.
The researchers analyzed randomized clinical trials that compared GLP-1s to placebo in children and adolescents with obesity, overweight, prediabetes, and/or T2D. Studies lacking both efficacy and safety outcomes were excluded.
Primary efficacy outcomes included change in A1C, fasting glucose, body weight, BMI, BMI percentile, BMI SDS, lipid outcomes, and BP. The safety outcome measures were GI adverse effects, infections, hepatobiliary disorders, suicidal ideation or behaviors, depression, hypoglycemia, and adverse event discontinuations.
No significant difference in depression was found between the GLP-1 group and the placebo group. There was a nonsignificant decrease in suicidal behaviors and ideation for the GLP-1 group.
Overall, GI adverse effects increased for those in the GLP-1 group across 14 trials. The authors noted that in the T2D trials, no meaningful effect was observed. But in the obesity trials, there was a notable increase in GI adverse effects in the GLP-1 versus the placebo group.
A total of 18 studies with 1,402 participants were included in the review. The patient age ranged from 6 to 17 years old, 59% were female, and nearly 68% were white.
The review incorporated studies published between 2023 and 2025.
Strength and weakness
Kotecha acknowledged that by including clinical trials that enrolled children as young as 6 years old, the meta-analysis broadens prior reviews, which focused on children and adolescents aged 10 years and up.
“Importantly, it brings together trial-based evidence on depression and suicidal ideation or behaviors—outcomes for which systematic review and meta-analysis data have remained limited in children and adolescents,” she said.
However, the researchers reported limitations of their systematic review. As depression and suicidal behaviors or ideation were not primary outcomes found in the included trials, the possibility exists for low precision and underreporting. Using aggregated data, instead of individual participant data, limited subgroup analysis.
The authors suggested that future trials “could assess treatment adherence with respect to patient preferences (e.g., problems with self-management related to injectables or cost) and their effect on safety (severity of gastrointestinal and other adverse events) and efficacy/effectiveness outcomes.”
“[Longer] follow up from future RCTs and real-world studies is essential to establish the long-term effects of [GLP-1s] in children and adolescents,” they concluded.
Kotecha said treatment decisions regarding GLP-1s in youth should be made collaboratively between patients, families, and the health care team.
“Pharmacists can support families by helping them understand where [GLP-1s] fit within this broader treatment framework, what is known from the evidence, and why ongoing monitoring and follow up with the prescribing clinician are important,” she said. ■