Commentary calls for pediatric safety research on tirzepatide in youth type 2 diabetes

A commentary published August 25, 2026 in AME Clinical Trials Review argues that tirzepatide showed real promise in children and adolescents with type 2 diabetes, but that the field needs dedicated safety research on growth, puberty, bone accrual and long-term adherence instead of relying on adult data ^[1].

The commentary reviews SURPASS-PEDS, a phase 3 randomized, double-blind, placebo-controlled trial published in The Lancet in 2025. It enrolled 99 participants aged 10 to under 19 who took 5 mg or 10 mg of tirzepatide, or a placebo, for 30 weeks ^[1].

Averaged across the two treatment groups, tirzepatide lowered HbA1c by 2.23 percentage points, while HbA1c rose by 0.05 points in the placebo group ^[1]. In the 5 mg and 10 mg groups, 71% and 86% of participants reached an HbA1c of 6.5% or below, the threshold used to define diabetes, compared with 28% on placebo. And 47% and 60% reached 5.7% or below, the normal range, compared with 14% on placebo ^[1].

Fasting glucose and BMI also improved, with larger effects at 10 mg. Weight fell 7.4% with 5 mg weekly and 11.2% with 10 mg weekly, close to the 7.9% and 9.3% seen with the same doses of tirzepatide in the adult SURPASS study ^[1]. Earlier pediatric trials of the GLP-1 receptor agonists liraglutide, exenatide and dulaglutide lowered HbA1c by 0.8% to 1.5% but did not show the same weight effect seen in adults ^[1].

The most common side effect was mild-to-moderate gastrointestinal upset that improved over time, and the safety profile was comparable to what has been seen in adults ^[1]. Participants were enrolled in eight countries: Australia, Brazil, India, Israel, Italy, Mexico, the UK and the USA. A 22-week open-label extension followed, during which the placebo group received 5 mg of tirzepatide ^[1].

What the commentary says is still unknown

Tirzepatide treatment reduced age- and sex-standardized BMI by 0.5 and 0.8 standard deviations for the 5 mg and 10 mg groups. Because BMI combines fat and fat-free mass, the authors write that the drop may reflect lost lean mass as well as, or instead of, lost fat ^[1]. In SURMOUNT-1, a 73-week trial of 2,539 adults with obesity, 25% of the weight reduction came from muscle mass ^[1].

The timing concerns the authors most. During puberty, 40% to 60% of adult bone mass is accumulated, and 25% of peak bone mass is gained in a two-year window around peak height velocity, which occurs around ages 11.5 to 12 for girls and 13.5 to 14 for boys. By age 18, 90% of peak bone mass has been accrued ^[1].

Little is known about the long-term effects of GIP and GLP-1 receptor agonist treatment in youth, including on the tempo of maturation and linear growth, fertility, neurocognition, eating behaviors and mental health ^[1]. A retrospective cohort study of about 150,000 singleton pregnancies with deliveries between 2016 and 2025 found higher risks of excessive gestational weight gain, gestational diabetes, hypertensive disorders and preterm delivery among women who used GLP-1 receptor agonists before conception or in early pregnancy and then discontinued them, compared with matched controls ^[1].

A sample of 99 people was too small to allow subgroup analysis, and the trial required participants to already be taking metformin at 1,000 mg/day or more, or basal insulin, which means it captured youth with more severe and longer-lasting disease. The full 15 mg dose was not tested in children, so safety across the full dosage range remains unknown ^[1].

Why it matters for patients

Tirzepatide is not approved for type 2 diabetes in children in the United States ^[1]. The commentary's core message is that a 30-week trial can establish short-term benefit while leaving open whether that benefit lasts and whether it interacts with the years when children build bone and muscle. The authors note that unlike bariatric surgery, which appears to have more durable effects in youth with type 2 diabetes, the benefits of these drugs diminish after treatment is stopped, so long-term treatment would likely be required ^[1].

Access is a separate issue the authors raise. High costs, limited insurance coverage and other structural factors lead to disparities in who gets prescriptions, particularly for low-income, rural and racial and ethnic minority patients, even when the drug is known to work ^[1].

What happens next

The commentary calls for larger and more racially and ethnically diverse studies, research on muscle mass and bone density in youth, and work on the safety and ideal duration of treatment and of stopping it, including outside pregnancy ^[1]. It does not describe a timeline for new trials or any upcoming regulatory decision on pediatric use ^[1].