STEP-1: Semaglutide Treatment Effect in People with Obesity — 1

Background + significance

STEP-1 was the first phase-3 trial of semaglutide 2.4 mg weekly for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity. Mean baseline weight was 105.3 kg. The 14.9% mean weight loss substantially exceeded any prior anti-obesity drug at the time, and led directly to Wegovy FDA approval in 2021.

Trial design

Sponsor

Novo Nordisk

Phase

Phase 3

Participants

1,961

Duration

68 weeks

ClinicalTrials.gov ID

NCT03548935

Drugs tested

• Wegovy (semaglutide 2.4 mg)Active

Primary outcome

Percentage change in body weight from baseline to week 68

−14.9% mean body-weight reduction on semaglutide vs −2.4% placebo (P<0.001)

Secondary outcomes

• •~70% of patients achieved ≥10% weight loss
• •~32% achieved ≥20% weight loss
• •Reduced waist circumference, systolic BP, A1C
• •Improvements in physical function (SF-36)

Why it matters

1. 1.STEP-1 is the foundational efficacy trial for Wegovy. Any "Wegovy works" claim ultimately cites STEP-1.
2. 2.About 1 in 3 patients reached ≥20% weight loss; about 1 in 6 lost less than 5% (real biological variance).
3. 3.Largest dropouts were GI side effects (nausea, vomiting) concentrated in weeks 1-4.