PMID-40961953 — STEP UP T2D: Semaglutide 7.2 mg in Obesity + T2D (Phase 3b, Lancet Diabetes Endocrinol 2025)

[DRAFT — authored 2026-04-20. Citation verified against PubMed/Lancet Diabetes Endocrinol 2026-04-20.]

Citation

Lingvay I, Blüher M, Davies MJ, Deanfield J, Garvey WT, Hansen TL, Hesse D, Jastreboff AM, Kushner RF, Rubino D, Wadden TA, Wharton S, Busetto L; STEP UP T2D Trial Group. Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):935-948. doi: 10.1016/S2213-8587(25)00235-5. PMID: 40961953. NCT05649137.

External URL: PubMed

Study Design

Design: Randomised, double-blind, placebo-controlled, parallel-group Phase 3b trial
Setting: 68 sites across 8 countries
N: 512 participants (7.2 mg: 307; 2.4 mg: 103; placebo: 102)
Population: Adults with BMI ≥27 kg/m² + type 2 diabetes
Baseline: Mean age 56, mean BMI 38.6 kg/m², mean baseline HbA1c 8.1%
Intervention: Once-weekly SC semaglutide 7.2 mg, 2.4 mg, or placebo
Duration: 72 weeks
Primary endpoint: Percent change in body weight at week 72

Key Findings

Weight loss at 72 weeks

Semaglutide 7.2 mg: −13.2%
Placebo: −3.9%
Mean bodyweight reduction difference vs placebo: −9.3 percentage points

Secondary outcomes

≥5% weight loss: 10-fold higher odds with 7.2 mg vs placebo
Waist circumference: −6.5 cm greater reduction with 7.2 mg
HbA1c: −1.5% greater reduction with 7.2 mg (substantial glycemic effect)

Safety

GI adverse events: 53% (7.2 mg) vs 26% (placebo)
Dysesthesia: 18.9% (7.2 mg) vs 4.9% (placebo) — elevated but lower than non-T2D STEP UP (22.9%)

Clinical Relevance

STEP UP T2D extends the STEP UP (non-T2D) finding to the T2D + obesity population, establishing that semaglutide 7.2 mg produces substantial weight loss and glycemic improvement in T2D + obesity. Core teaching points:

Weight loss magnitude lower in T2D (−13.2%) than non-T2D (−18.7%) — consistent with the STEP 1/STEP 2 pattern (T2D patients typically achieve smaller weight-loss magnitude than non-T2D at the same semaglutide dose).
HbA1c −1.5% is a substantial glycemic effect — may support T2D-label extension at 7.2 mg dose in future regulatory cycles.
Lower dysesthesia rate (18.9%) vs non-T2D (22.9%) — possible signal attenuation in T2D population, though mechanism unclear.
FDA Wegovy 7.2 mg approval (March 19, 2026) is currently for obesity indication only — T2D extension would require separate regulatory filing beyond the non-T2D obesity label.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (Wegovy HD section, T2D context)

Related Studies

PMID-40961952 – STEP UP Wharton Semaglutide 7.2 mg Obesity — non-T2D companion trial
REG-FDA-Wegovy-HD-2026 – Wegovy 7.2 mg National Priority Voucher Approval — FDA approval
PMID-33667417 – STEP 2 Semaglutide in T2D Obesity — STEP 2 (2.4 mg) comparator in T2D

PMID-40961953 – STEP UP T2D Lingvay Semaglutide 7.2 mg