VIENNA — Tirzepatide leads to clinically meaningful improvements in blood sugar levels and weight loss in children and adolescents whose type 2 diabetes is inadequately controlled, according to results from the first randomized trial of the dual glucose-dependent insulinotropic polypeptide/GLP-1 in this population.

A1c reductions were sustained to week 52, and tirzepatide is the first therapy to demonstrate significant and durable BMI reductions in youth with type 2 diabetes.

Overall, tirzepatide was well tolerated with a safety profile consistent with tirzepatide in adults with type 2 diabetes and other studies of GLP-1s in children and adolescents with type 2 diabetes.

Results of the SURPASS-PEDS trial were presented at the European Association for the Study of Diabetes (EASD) 2025 Annual Meeting and were also simultaneously published in The Lancet.

“Tirzepatide is the first drug in this age group to show sustained, clinically meaningful reductions in BMI,” said lead investigator Tamara Hannon, MD, pediatric endocrinologist at Indiana University School of Medicine, Indianapolis. “These results support it as a potential safe and effective treatment option for youth-onset type 2 diabetes.”

Hannon said the findings will likely resonate with clinicians. “I think many doctors will welcome this drug for treating type 2 diabetes in children because with currently approved medications it’s very difficult to achieve A1c targets of less than 6.5%,” she remarked.

“If we want to prevent long-term macrovascular and microvascular complications, we need glucose-lowering therapies, and here we see really significant glucose lowering,” she added. “Of course, these results only extend to 1 year, and these children will live with diabetes their whole lives. But I think this drug will be in high demand.”

Paucity of Treatment Options in Children With Type 2 Diabetes

Hannon explained there are fewer approved glucose-lowering treatment options for youth with type 2 diabetes than adults, with current treatment options including metformin, insulin, three GLP-1s, and two SGLT2 inhibitors. “Generally, available treatments have less glycemic efficacy and a higher rate of treatment failure compared to adults, and there is no approved therapy in youth that has shown a clinically meaningful effect on body weight or BMI reduction compared with placebo.”

The phase 3, double-blind, placebo-controlled study was held at 39 sites in eight countries. A total of 99 participants were randomized (1:1:1) to receive tirzepatide 5 mg, 10 mg, or placebo once weekly, administered by subcutaneous injection for 30 weeks, followed by an open-label extension (5 mg weekly) for 22 weeks in which all participants received tirzepatide.

Participants were between 10 and 18 years old — with slightly more in the 15 years or older age-stratified group — and overall, 60% were female. Overall duration of type 2 diabetes was a mean of 2.4 years inadequately controlled with metformin (68%) and/or basal insulin (23% and 8%, respectively). In addition to age bracket, randomization was stratified by medication — metformin, basal insulin, or both. Mean A1c was 8.04%. The primary endpoint was the change in A1c from baseline to week 30, according to data from participants who had received at least one dose of tirzepatide. Safety was also assessed.

Glycemic Control and BMI Outcomes

Around 90% of participants completed the study across the three groups. The estimated treatment difference in A1c from baseline to week 30 in the pooled data (5 mg plus 10 mg) and placebo was -2.28% (P < .001). A1c improvements were sustained to week 52, with mean levels of 5.8%.

For BMI, pooled tirzepatide groups showed a placebo-adjusted reduction of -0.54 at week 30 (P < .001). At week 52, BMI decreased by 8.9% with 5 mg and 15.1% with 10 mg. Waist circumference, triglycerides, low-density lipoprotein, and blood pressure also improved relative to placebo. Overall mean waist circumference at baseline was 106.1 cm, and the pooled tirzepatide results showed a drop of 10.28 cm by 52 weeks. “Tirzepatide is the only treatment to demonstrate significant and clinically meaningful reduction in BMI in youth with type 2 diabetes,” added Hannon.

Finally, for weight loss between baseline and week 30, the pooled data showed a body weight change of mean -9.07% (P < .001). Body weight in the pooled data at week 52 was 85.5 kg.

Mild-to-Moderate Gastrointestinal Adverse Events

Overall, tirzepatide was well tolerated with a safety profile consistent with tirzepatide in adults with type 2 diabetes and other studies of GLP-1 receptor agonists in children and adolescents with type 2 diabetes.

The most common adverse events were gastrointestinal, all mild-to-moderate in severity, and occurred mostly during dose escalation and decreased over time. Treatment discontinuation due to adverse events occurred in 6.3% of participants in the tirzepatide 5-mg group and 0% in the tirzepatide 10-mg and placebo groups. No severe hypoglycemia episodes were reported during the study.

Hannon added, “The rate of level 2 hypoglycemia (BG [blood glucose] < 54 mg/dL) was higher in tirzepatide-treated participants compared with placebo, with the highest rate in those treated with a background of basal insulin.”

The Lancet paper also reported no deaths, no pancreatitis, and no differences in pubertal progression or growth metrics.

Expert Commentary: A ‘Well-Conducted’ Study

Session moderator Melanie Davies shared her thoughts on the results with Medscape Medical News, stressing that it was “a very important and well-conducted global trial in a group of patients currently underserved and underrepresented in clinical trial programs — children and young people living with type 2 diabetes,” and pointed out, “We have few available treatments, so it is timely to have this data.”

She welcomed the inclusion of around half of participants being younger — aged 10-14 years. “The investigators should be congratulated on the good recruitment and retention, as while type 2 diabetes is increasing in this age group, it is often challenging to recruit into these interventional trials.”

“The A1c decline of 2.28% compared with placebo is impressive and appears sustained out to 52 weeks, and the safety profile looks reassuring and impact on weight and cardiovascular risk factors too,” she said, adding, “We do need larger and longer-duration trials in this young population to really see the longer-term benefits and safety, but this trial is a really important milestone in the field.”

Hannon reported receiving grant support from the National Institute of Diabetes and Digestive and Kidney Diseases and the Eli Lilly Foundation, consulted for Eli Lilly and Company, and was a trial site investigator for Eli Lilly and Company and Novo Nordisk. Davies reported declaring relevant financial relationships: Advisory Panel: AbbVie, Amgen, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Carmot/Roche, EktaH, GSK, Regeneron, Sanofi-Aventis, and Zealand Pharma; Consultant: Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, and Sanofi-Aventis; Research Support: AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; Speakers Bureau: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, and Sanofi-Aventis.