Tirzepatide Lowers A1C and BMI in Children and Adolescents with Type 2 Diabetes

SURPASS-PEDS, the first phase 3 trial of GIP/GLP-1 dual receptor agonist tirzepatide (Mounjaro; Eli Lilly) in children and adolescents with type 2 diabetes (T2D), met its primary and all secondary endpoints at 30 weeks, with sustained benefits through 52 weeks, according to data presented at the European Association for the Study of Diabetes (EASD) Annual Meeting, September 15-19, in Vienna, Austria, and published simultaneously in The Lancet.¹ The 10-mg dose of tirzepatide was associated with an average body mass index (BMI) reduction of 11.2% at the 30 week mark.

Tamara S Hannon, MD

Courtesy of Riley Children's Health

Investigators, led by Tamara Hannon, MD, director of the Clinical Diabetes Program at Indiana University School of Medicine, reported that tirzepatide, at 30 weeks, reduced HbA1c by an average of 2.2% from a mean baseline of 8.05% using the efficacy estimand, compared with a 0.05% increase with placebo. The 10 mg dose lowered HbA1c by 2.3% and achieved the American Diabetes Association recommended target HbA1c of 6.5% or less in 86.1% of participants. For participants treated with placebo, just slightly more than one-quarter (27.8%) reached the target.¹

Weight and Glycemic Measures Improve

Hannon et al also reported important physical and other physiologic improvements. Tirzepatide reduced body mass index (BMI) from a baseline of 35.3 kg/m². The 10 mg dose lowered BMI by 11.2% on average, compared with a 0.4% reduction on placebo. The BMI standard deviation score decreased by 0.76 with 10 mg, compared with 0.09 with placebo.

Fasting serum glucose dropped by 53.5 mg/dL on the 10 mg dose, versus 7.9 mg/dL with placebo. Improvements in glycemic control and BMI continued through the trial’s 52-week open-label extension.¹

“Youth living with type 2 diabetes 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,” lead investigator Hannon said in a statement.² “The SURPASS-PEDS results show that Mounjaro delivered significant and clinically meaningful improvements in blood sugar, BMI and fasting serum glucose in pediatric patients. These results offer a promising opportunity to help shift the long-term health trajectory for young people living with this complex condition.”²

SURPASS-PEDS (NCT05260021) enrolled 99 participants ages 10 to younger than 18 years with T2D inadequately controlled on metformin, basal insulin, or both. At baseline, participants had an average HbA1c of 8.04%, BMI of 35.4 kg/m², weight of 96.6 kg, and diabetes duration of 2.4 years. The double-blind, placebo-controlled trial ran 30 weeks with a 22-week open-label extension in which all participants received tirzepatide.¹

Safety and Tolerability

The safety profile of tirzepatide in adolescents was generally consistent with previous adult studies and the incretin class overall. The team said the most common adverse events (AEs)were gastrointestinal and occurred mainly during dose escalation: diarrhea (25% vs. 6% placebo), nausea (20% vs. 9%), vomiting (14% vs. 3%), and abdominal pain (9% vs. 3%). Hannon et al described the severity of these AEs as mild-to-moderate. Treatment discontinuation due to adverse events occurred in 6% (5 mg), 0% (10 mg), and 3% (pooled tirzepatide) compared with 0% placebo.¹

There were no episodes of severe hypoglycemia, according to the study. Level 2 hypoglycemia (blood glucose <54 mg/dL) occurred in 15.4% of tirzepatide-treated participants vs 5.9% with placebo. The study authors noted these rates are consistent with those seen in other youth-onset type 2 diabetes trials.¹

“Type 2 diabetes in children and teens is increasing at an alarming rate, yet treatment options are limited, and this patient population remains underserved,” Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, said in a statement. “The SURPASS-PEDS results show [tirzepatide] delivered statistically significant improvements in [HbA1c], BMI and other critical cardiometabolic risk factors, while maintaining a safety profile generally consistent with adult studies.”²

Recent data document a sharp rise in T2D among children and adolescents. A US study covering 2001 to 2017 found that among youths aged 10-19 years, the prevalence of T2D increased from 0.34 per 1,000 in 2001 to 0.67 per 1,000 in 2017, a relative increase of about 95.3%.³

These trends occur disproportionately among racial and ethnic minority youth. For example, annual incidence of T2D rose most steeply in Native American, non-Hispanic Black, Hispanic, and Asian/Pacific Islander youths.⁴

Lilly has submitted these results to global regulatory agencies for an expanded indication for tirzepatide in youth with T2D.²

References

1. Hannon TS, Chao LC, Barrientos-Perez M, et al. Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online September 17, 2025. doi:10.1016/S0140-6736(25)01774-X

2. 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. News release. September 17, 2025. Accessed September 18, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-receptor-agonist

3. Lawrence JM, Divers J, Isom S, et al. Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2000-2017. JAMA. 2021;326;(8):717-727. doi:10.1001/jama.2021.11165

4. Trends in diabetes among young people. Centers for Disease Control and Prevention. May 15, 2024. Accessed September 18, 2025. https://www.cdc.gov/diabetes/data-research/research/trends-new-diabetes-cases-young-people.html