Tirzepatide cut HbA1c by 2.23 points in youth with type 2 diabetes, phase 3 trial finds

The Lancet has published results from SURPASS-PEDS, a phase 3 trial in which tirzepatide lowered HbA1c by a mean of 2.23 percentage points in children and adolescents with youth-onset type 2 diabetes, compared with a 0.05-point rise in the placebo group at 30 weeks ^[1][2].

The trial enrolled 99 participants with a mean age of 14.7 years (standard deviation 1.8) at 39 sites in eight countries. Everyone was between 10 and under 18 years old and had type 2 diabetes that was not adequately controlled with metformin, basal insulin, or both. Participants were randomly assigned in equal groups to tirzepatide 5 mg (32 people), tirzepatide 10 mg (33), or placebo (34), given as a subcutaneous injection with a single-dose pen. Sixty participants (61%) were female and 39 (39%) were male, and the mean baseline HbA1c was 8.04% ^[1][2].

At week 30, the estimated treatment difference between the pooled tirzepatide groups and placebo was -2.28 percentage points (95% CI -2.87 to -1.69; p<0.0001). Body mass index fell 7.4% in the 5 mg group and 11.2% in the 10 mg group, compared with 0.4% in the placebo group. The authors report that glycemic efficacy was sustained up to 52 weeks. After the 30-week double-blind period, the trial continued with a 22-week open-label extension in which all participants received tirzepatide ^[1][2].

Gastrointestinal adverse events were the most common with tirzepatide, were mild to moderate in severity, and decreased over time. Two participants (6%) in the 5 mg group stopped the study drug because of an adverse event. No deaths were reported during the study period, and the safety profile was consistent with what has been reported in adults ^[1][2].

Enrollment ran from April 12, 2022, to Dec 27, 2023. The trial was funded by Eli Lilly and Company, which makes tirzepatide. Several authors are Lilly employees and shareholders, and some site investigators reported consulting for or receiving support from Lilly and Novo Nordisk ^[1][2]. The Lancet later published a correction notice for the paper ^[2].

Tirzepatide is the molecule in the medicines sold in the United States as Mounjaro and Zepbound.

Why it matters for patients

Youth-onset type 2 diabetes has had limited treatment options, and the trial authors note that existing medicines have shown lower glycemic efficacy in young people than in adults ^[1][2]. The 2.23-point average HbA1c reduction at 30 weeks is the central result for that age group.

That said, the study documents an effect in a population that may not currently be able to get the drug for this use. Mounjaro and Zepbound are approved for adults in the United States, and whether regulators extend approval to children and adolescents has not been announced in these results. The publication does not state whether Eli Lilly has filed for pediatric approval.

The trial followed participants for 30 blinded weeks plus a 22-week open-label extension, so effects and side effects in young people beyond roughly one year of treatment have not been reported. Because the participants are still growing, questions about longer-term effects on growth and development are also not answered by these results. The disclosure list shows that the funder and several authors have financial ties to the drug's manufacturer, which is standard for industry-sponsored trials but is worth knowing when reading the findings.

What happens next

The trial is registered with ClinicalTrials.gov (NCT05260021) and is described as completed ^[1][2]. Any regulatory decision on tirzepatide for pediatric type 2 diabetes, and any longer-term follow-up data in this age group, have not been disclosed.