GLP-1 RAs work well for managing T2D, obesity in children

Children and teens with type 2 diabetes (T2D) or obesity benefit from glucagon-like peptide-1 receptor agonists (GLP-1RAs), which help improve blood sugar and weight, according to a meta-analysis.

Pooled data from 18 randomized controlled trials showed that compared with placebo, GLP-1RAs yielded significant reductions in HbA_1c (estimated treatment difference [ETD], −0.44 percent, 95 percent confidence interval [CI], −0.68 to −0.21) and fasting plasma glucose (ETD, −9.92 mg/dL, 95 percent CI, −16.20 to −3.64). These effects were pronounced in T2D trials (ETD, –0.94 percent and –22.56 mg/dL) but less so in obesity trials (ETD, –0.10 percent and –1.39 mg/dL). [JAMA Pediatr 2025;doi:10.1001/jamapediatrics.2025.3243]

GLP-1RAs were also associated with more favourable improvements in weight-related parameters, including BMI (ETD, −1.45, 95 percent CI, −2.40 to −0.49), body weight (ETD, −3.02 kg, 95 percent CI, −4.98 to −1.06), waist circumference (ETD, −3.81 cm, 95 percent CI, −6.76 to −0.87), BMI percentile (ETD, −7.24 percent, 95 percent CI, −12.97 to −1.51), and BMI standard deviation score (ETD, −0.20, 95 percent CI, −0.36 to −0.05). However, these effects were significant only in the obesity trials.

For blood pressure (BP), substantial systolic BP reductions (ETD, –2.73 mm Hg, 95 percent CI, −4.04 to −1.43) and nonsignificant diastolic BP declines (ETD, −1.21 mm Hg, 95 percent CI, −2.81 to 0.39) were seen with GLP1-RAs. In terms of lipid outcomes, minimal changes were seen in total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride, and very low–density lipoprotein levels.

Exploratory analyses showed GLP-1RAs to have a nonsignificant effect on obstructive sleep apnoea in two obesity trials (log[rate ratio] [logRR], −0.70, 95 percent CI, −2.75 to 1.35) but no evidence of benefit for metabolic dysfunction-associated steatohepatitis and steatotic liver disease in one T2D trial (logRR, 0.24, 95 percent CI, −1.80 to 2.29).

In terms of safety, gastrointestinal adverse events (AEs) occurred more frequently with GLP-1RA vs placebo overall (logRR, 0.73, 95 percent CI, 0.38–1.07). No significant differences were seen in hepatobiliary outcomes (logRR, 0.07, 95 percent CI, −0.58 to 0.72), infections (logRR, 0.05, 95 percent CI, −0.13 to 0.23), depression (logRR, 0.02, 95 percent CI, −1.54 to 1.58), and suicidal ideation and behaviour (logRR, −0.46, 95 percent CI, −1.42 to 0.49).

GLP-1RAs showed a nonsignificant trend toward increased rates of hypoglycaemia compared with placebo (logRR, 0.51, 95 percent CI, −0.07 to 1.08). Similarly, treatment discontinuation due to AEs tended to occur more frequently with GLP1-RAs vs placebo, but this trend was not statistically significant (logRR, 0.39, 95 percent CI, −0.37 to 1.14).

“This systematic review and meta-analysis provides a comprehensive evaluation of the benefits and risks associated with GLP-1RAs in the paediatric population, enabling patients, caregivers, and clinicians to make more informed treatment decisions,” the investigators said.

Additional clinical trials and real-world studies are needed to build on the present findings, assess treatment adherence with respect to patient preferences, and establish the drugs’ safety and long-term effect, they added.

Of the 18 trials included in the meta-analysis, 11 were in obesity, six in T2D, and one in prediabetes. They involved a total of 1,402 children (mean age 13.7 years, 59.3 percent female, 67.9 percent White), of which 838 received GLP-1RA and 564 placebo. The median treatment duration was 0.51 years, while the median follow-up duration was 0.19 years.