Tirzepatide lowers HbA1c, BMI in youth-onset T2D

Once-weekly treatment with tirzepatide significantly reduces HbA_1c levels and BMI in children and adolescents with type 2 diabetes (T2D) compared with placebo, according to the SURPASS-PEDS trial presented at EASD 2025.

“Youth-onset T2D (YT2D) is a more aggressive disease compared with adults. It is marked by much higher insulin resistance and a more rapid decline in beta cell function requiring more treatment with insulin,” said lead author Dr Tamara Hannon from the Department of Pediatrics, Division of Pediatric Endocrinology, Indiana University School of Medicine in Indianapolis, US.

Unfortunately, “there are fewer approved glucose-lowering treatment options for YT2D compared with adults … and no approved therapy in youth has demonstrated a clinically meaningful effect on body weight or BMI reduction,” she added.

The SURPASS-PEDS trial included 99 participants (mean age 14.7 years, 60 percent female), of whom 44 percent were aged ≥10 to <14 years and 55 percent were aged ≥15 to <18 years, with inadequately controlled YT2D despite treatment with metformin (68 percent), basal insulin (8 percent), or both (23 percent).

At baseline, the mean HbA_1c level was 8.04 percent, fasting glucose level was 152 mg/dL, and the mean BMI was 35.4 kg/m², with a body weight of 96.6 kg.

During the double-blind period, participants were randomized in a 1:1:1 ratio to receive tirzepatide weekly (n=32 [5 mg] or n=33 [10 mg]) or an injectable placebo (n=34) for 30 weeks. Subsequently, those initially on placebo were switched to tirzepatide 5 mg weekly during the open-label period. [Hannon T, et al, EASD 2025]

At week 30, the pooled tirzepatide group demonstrated a significantly greater reduction in HbA_1c levels from baseline compared with the placebo group (estimated treatment difference [ETD], -2.28 percent; p<0.001), which was sustained through week 52 (ETD, -2.21 percent).

As for the individual results, both tirzepatide 5- and 10-mg doses showed superiority over placebo in reducing HbA_1c levels, with ETDs of -2.21 percent and -2.35 percent, respectively.

Significantly more patients in the pooled tirzepatide group achieved the glycaemic target of HbA_1c <6.5 percent by week 30 (78.6 percent vs 27.8 percent; p<0.001) and maintained this at week 52 (79.4 percent vs 60 percent) than those in the placebo group.

In addition, more than half of the patients achieved a normal HbA_1c level of <5.7 percent at weeks 30 and 52 (53.4 percent vs 14.4 percent and 52.4 percent vs 39 percent, respectively) compared with the placebo recipients.

Pooled tirzepatide group also had a greater decline in fasting serum glucose (FSG) from baseline to week 30 (ETD, -36.3 mg/dL; p<0.001) and 52 (ETD, -44 mg/dL) than those in the placebo group.

At week 52, the mean BMI was reduced by 8.9 percent in the tirzepatide 5-mg group and 15.1 percent in the 10-mg group compared with 4.8 percent in the placebo group. Notably, “BMI reduction did not appear to plateau … indicating that participants were still losing weight at the end of the trial,” according to Hannon.

In terms of safety, adverse events (AEs) of any grade occurred in 68 percent of the pooled tirzepatide group and 44 percent of the placebo group.

The most common AEs associated with tirzepatide were diarrhoea (25 percent), nausea (20 percent), vomiting (14 percent), and abdominal pain or discomfort (9 percent), but all were classified as mild to moderate in severity.

No cases of severe hypoglycaemia were observed during the study, Hannon noted.

“Overall, in children and adolescents (10 to <18 years) with T2D, tirzepatide demonstrated superiority vs placebo in mean change from baseline in HbA_1c, FSG, and percentage change in BMI,” said Hannon. “Tirzepatide was well tolerated with a safety profile consistent with tirzepatide in adults with T2D and other studies of GLP-1 receptor agonists in YT2D,” she added.

Invited discussant Dr Agnieszka Szadkowska from Medical University of Lodz, Poland, who is unaffiliated with the study, commented that “the results of the study showed that tirzepatide, once approved, could become one of the first-line drugs for treating children with T2D … and the inclusion of this drug should be considered especially in children with obesity.”