Commentary sets research priorities for tirzepatide in youth with type 2 diabetes

A commentary published in AME Clinical Trials Review reviewed results from SURPASS-PEDS, a phase 3 trial testing tirzepatide in adolescents and children with type 2 diabetes, and concluded the drug shows clinical promise but leaves important safety questions unanswered for young patients ^[1]. Tirzepatide, sold as Mounjaro and Zepbound for adults, is not approved for type 2 diabetes in children in the United States ^[1].

In the underlying trial, tirzepatide at 5 mg or 10 mg weekly lowered HbA1c by an average of 2.23% over 30 weeks in participants ages 10 to under 19, compared with a 0.05% increase in the placebo group ^[1]. Roughly 71% of youth on 5 mg and 86% on 10 mg brought HbA1c below the diabetes threshold of 6.5%, versus 28% on placebo ^[1]. Weight loss was substantial too: 7.4% with the 5 mg dose and 11.2% with the 10 mg dose, numbers the commentary says are similar to what adults experienced on the same doses in the SURPASS-1 adult trial ^[1]. The most common side effect was mild to moderate gastrointestinal upset that improved over time ^[1].

The commentary's authors, however, raised several concerns. They noted that the trial's body mass index reductions could reflect loss of lean muscle mass rather than only fat, a worry because adolescence is a critical window for building muscle and bone ^[1]. The authors point out that 40% to 60% of adult bone mass accumulates during puberty, and by age 18 about 90% of peak bone mass has been laid down ^[1]. Because muscle mass strongly influences bone density, unintended muscle loss during these years could carry lifelong consequences, according to the commentary ^[1].

The authors also flagged that SURPASS-PEDS enrolled only 99 participants, too few to break down results by subgroup, and that eligibility required participants already be on high-dose metformin or insulin, meaning the trial captured youth with more severe disease ^[1]. The full 15 mg dose tested in adults was not studied in this trial, so its safety profile in youth remains unknown ^[1]. The commentary also cited a separate retrospective study of about 150,000 pregnancies that found higher rates 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 stopped, as current guidance recommends, compared with matched controls ^[1].

Why it matters for patients

For families of adolescents with type 2 diabetes, the commentary underscores that while short-term blood sugar and weight results from SURPASS-PEDS were strong, tirzepatide is not currently approved for this age group in the U.S., and questions about its effects on growth, puberty, bone strength, and long-term treatment remain open ^[1]. The authors specifically called for follow-up studies rather than assuming that adult safety data apply directly to children, since adolescents are still developing muscle and bone in ways adults are not ^[1].

The commentary also raised a broader access concern: because GLP-1 and GIP receptor agonist drugs likely require long-term use to sustain benefits—unlike bariatric surgery, which the authors describe as having more durable effects in youth with type 2 diabetes—high costs and uneven insurance coverage could worsen existing disparities in diabetes care for low-income, rural, and minority families if the drugs are eventually approved for children ^[1].

What happens next

The commentary calls for dedicated pediatric safety studies focused on bone density, muscle mass, growth timing, fertility, and mental health outcomes, along with larger and more diverse trials to understand how different patients respond ^[1]. No specific timeline for additional pediatric trials or a U.S. approval decision was given in the sources reviewed.