SURPASS-PEDS: Tirzepatide Achieves Superiority to Placebo in Adolescent T2D

Tirzepatide (Mounjaro) met the primary and all key secondary endpoints in the phase 3 SURPASS-PEDS trial, achieving superior improvements in both A1C and body mass index (BMI) versus placebo in adolescents with type 2 diabetes (T2D).1

Presented by parent company Eli Lilly and Company at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025, SURPASS-PEDS is the first phase 3 trial evaluating the safety and efficacy of tirzepatide in children and adolescents, ages 10-18, with T2D inadequately controlled with metformin, basal insulin, or both. Tirzepatide had achieved its endpoints by week 30.1

Eli Lilly’s Mounjaro was first approved by the US Food and Drug Administration (FDA) in May 2022 as an injection for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D). At the time, it was the first and only FDA-approved GIP/GLP-1 receptor agonist.2

“Youth living with T2D often face a more aggressive disease course, and in many instances, first-line treatments like metformin and basal insulin fail to control their A1C adequately,” Tamara Hannon, MD, director of the Clinical Diabetes Program at the Indiana University School of Medicine and lead investigator in the trial, said in a statement. “The SURPASS-PEDS results show that [tirzepatide] delivered significant and clinically meaningful improvements in blood sugar, BMI, and fasting serum glucose in pediatric patients.”1

SURPASS-PEDS is a regulator-required, multicenter, randomized, double-blind, placebo-controlled trial with an open-label extension. Investigators randomly assigned 99 participants to either tirzepatide 5mg, 10mg, or placebo once weekly. The primary endpoint was to prove tirzepatide’s superiority to placebo in mean A1C change from baseline after 30 weeks.1

Included patients weighed ≥50 kg, had an A1C of >6.5% to ≤11% at screening, and BMI >85th percentile of the general age- and gender-matched population for the corresponding country or region. Average baseline A1C among the participants was 8.04%, average BMI was 35.4 kg/m2, and average baseline weight was 96.6 kg. Average baseline BMI standard deviation score was 3.11 and average diabetes duration was 2.4 years.1

Ultimately, pooled tirzepatide doses lowered A1C by an average of 2.2% from baseline. A key secondary endpoint highlighted 86.1% of participants assigned to tirzepatide 10mg achieved a target A1C of ≤6.5%. Additionally, tirzepatide saw clinically meaningful improvements in BMI, with the 10mg dose reducing it by 11.2% on average at 30 weeks. Improvements continued through the long-term extension of 52 weeks.1

Investigators also noted the consistency of the safety profile with the established incretin class, including data from the previous SURPASS trials. The most common adverse events for patients receiving tirzepatide 5mg, 10mg, and pooled doses respectively were diarrhea (25%, 24%, and 25% vs 6% with placebo), nausea (22%, 18%, and 20% vs 9% placebo), vomiting (16%, 12%, and 14% vs 3% with placebo), and abdominal pain (16%, 3%, and 9% vs 3% with placebo). No episodes of severe hypoglycemia were observed.1

“The SURPASS-PEDS results show [tirzepatide] delivered statistically significant improvements in A1C, BMI, and other critical cardiometabolic risk factors, while maintaining a safety profile generally consistent with adult studies,” Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, said in a statement. “By undertaking this research, we can better support children and adolescents living with this condition.”1

In the same press release, Lilly announced submission of the SURPASS-PEDS results to global regulatory agencies, seeking an expanded indication.1

References

1. Lilly’s Mounjaro (tirzepatide), a GIP/GLP-1 dual receptor agonist, reduced A1C by an average of 2.2% in a Phase 3 trial of children and adolescents with type 2 diabetes. Eli Lilly and Company. September 17, 2025. Accessed September 18, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-receptor-agonist

2. FDA approves Lilly’s Mounjaro (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Eli Lilly and Company. May 13, 2022. Accessed September 18, 2025. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-mounjarotm-tirzepatide-injection-first-and#:~:text=News%20Release-,FDA%20approves%20Lilly's%20Mounjaro%E2%84%A2%20(tirzepatide)%20injection%2C%20the%20first,with%20type%201%20diabetes%20mellitus