PMID-40975112 — SURPASS-PEDS: Tirzepatide in Youth T2D (Phase 3)

[DRAFT — authored 2026-04-19. Citation web-verified 2026-04-19 against PubMed.]

Citation

Hannon TS, 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. 2025;406(10511):1484-1496. doi: 10.1016/S0140-6736(25)01774-X. PMID: 40975112.

External URL: DOI resolver

Study Design

Phase: 3
Design: Multicenter, randomised, double-blind, placebo-controlled
Randomization: To tirzepatide 5 mg weekly, tirzepatide 10 mg weekly, or matching placebo
Duration: Primary endpoint at week 30; sustained-effect assessment over 52 weeks
N: 99 youth participants
Mean age at enrollment: 14.7 years
Background therapy: Participants were inadequately controlled on metformin and/or basal insulin

Population

Children and adolescents (10-17 years at enrollment) with youth-onset type 2 diabetes
Inadequate glycemic control on background standard therapy (metformin ± basal insulin)

Intervention

Tirzepatide: 5 mg or 10 mg weekly SC, titrated per adult SURPASS protocol
Placebo: Matching weekly SC injection
Background metformin and/or basal insulin continued

Outcomes

Primary — HbA1c change at week 30

Tirzepatide (pooled active arms): HbA1c change -2.23% (approximate, pooled)
Placebo: HbA1c change +0.05% — essentially unchanged
Between-group difference: Large, statistically significant improvement in glycemic control with tirzepatide

Secondary

BMI: Significant reductions vs placebo, sustained over time
Fasting glucose: Improved dose-responsively
Insulin dose: Reductions in concomitant basal insulin requirements in insulin-treated participants
Safety: Adverse-event profile consistent with adult SURPASS program — predominantly GI (nausea, vomiting, diarrhea); dose-responsive

Key Findings

SURPASS-PEDS establishes tirzepatide as a safe and highly effective glycemic and BMI-reducing therapy for youth with type 2 diabetes — paralleling adult SURPASS efficacy and safety findings. Core teaching points:

The ~2.3% HbA1c reduction is substantially larger than what metformin alone achieves in youth T2D and is clinically transformative for this population
BMI reduction supports tirzepatide's dual role in glycemic control and obesity management in a pediatric population where both are often inadequately addressed
Safety profile consistent with adult data — GI tolerability is the primary limiter; no new pediatric-specific safety signals reported
First Phase 3 trial of tirzepatide in pediatric T2D — fills a long-standing evidence gap in youth-onset T2D treatment

Clinical Relevance

Youth-onset T2D is a progressive disease with faster decline in pancreatic function and higher complication rates than adult-onset T2D. The evidence base has historically been sparse — metformin and basal insulin have been the mainstays, with limited options for advancing therapy in inadequately controlled patients.

SURPASS-PEDS supports:

Tirzepatide 5-10 mg weekly as advancing therapy in adolescents with T2D inadequately controlled on metformin ± basal insulin
ADA and international pediatric-diabetes guidelines incorporating this evidence
Specialty-pediatric-endocrinology-directed initiation given the unique considerations in this age group

Companion pediatric evidence:

Semaglutide in adolescents with obesity (not T2D): PMID-36322838 – STEP TEENS Semaglutide Adolescents — STEP TEENS (Weghuber 2022).

Limitations (Author-acknowledged)

Modest sample size (n=99); larger studies may refine effect-size estimates
Primary endpoint at 30 weeks; 1-year data presented, longer-term durability still accumulating
Developmental and reproductive safety in long-term pediatric exposure not yet fully characterized
Generalizability across youth-T2D phenotypes (e.g., non-obese, type 2 subtypes) requires care

Evidence Level

Level Ib (Oxford CEBM) — adequately-powered Phase 3 RCT with pre-specified primary endpoint in a specific population.

Linked Peptides

Tirzepatide

Related Studies

PMID-36322838 – STEP TEENS Semaglutide Adolescents (semaglutide in adolescent obesity — companion pediatric evidence)
PMID-35658024 – SURMOUNT-1 Tirzepatide for Obesity (adult SURMOUNT benchmark)

Orchestrator Notes

Citation web-verified 2026-04-19 via PubMed.
Primary evidence for Tirzepatide profile special-populations (pediatric / adolescent T2D) section.
Cross-reference companion for Semaglutide STEP TEENS (adolescent obesity).

PMID-40975112 – SURPASS-PEDS Tirzepatide Youth