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Semaglutide · Phase 3 · Completed

STEP 3

In STEP 3, a phase 3 trial of semaglutide in US adults without diabetes with overweight (BMI 27 or greater) plus at least 1 comorbidity or obesity (BMI 30 or greater) (n=611), mean body weight fell 16.0% on 2.4 mg over 68 weeks, against 5.7% on placebo (treatment-policy estimand; Wadden TA et al. JAMA 2021 (STEP 3)).

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Results

STEP 3: mean percent change in body weight by armSTEP 3 treatment-policy estimand2.4 mg-16.0%Placebo-5.7%
Mean percent change in body weight by arm, as each source reports it. Bars from different trials are not a head-to-head comparison: populations, durations and estimands differ.

Side effects reported

In STEP 3, discontinuation because of adverse events was 5.9% on 2.4 mg, against 2.9% on placebo. The most frequently reported adverse events were gastrointestinal adverse events in 82.8% on 2.4 mg against 63.2% on placebo, nausea in 58.2% on 2.4 mg against 22.1% on placebo, constipation in 36.9% on 2.4 mg against 24.5% on placebo and diarrhoea in 36.1% on 2.4 mg against 22.1% on placebo.

Event2.4 mgPlacebo
Discontinuation for adverse events5.9%2.9%
Gastrointestinal adverse events82.8%63.2%
Nausea58.2%22.1%
Constipation36.9%24.5%
Diarrhoea36.1%22.1%
Vomiting27.3%10.8%

Design

Trial design and sources

Compound
Semaglutide
Phase
3
Population
US adults without diabetes with overweight (BMI 27 or greater) plus at least 1 comorbidity or obesity (BMI 30 or greater)
Participants randomised
611
Duration
68 weeks
Primary endpoint
Co-primary: percentage change in body weight and loss of 5% or more of baseline weight by week 68
Estimand
treatment-policy
Read out
1 April 2021

Discontinuation for adverse events is 5.9% against 2.9% in the safety section; the disposition paragraph gives 6.4% against 2.9%.

  • Wadden TA et al. JAMA 2021 (STEP 3) open · checked 23 September 2026
  • ClinicalTrials.gov NCT03611582 open · checked 23 September 2026
  • Registry: NCT03611582

Questions

STEP 3, answered

What did STEP 3 find?

In STEP 3, a phase 3 trial of semaglutide in US adults without diabetes with overweight (BMI 27 or greater) plus at least 1 comorbidity or obesity (BMI 30 or greater) (n=611), mean body weight fell 16.0% on 2.4 mg over 68 weeks, against 5.7% on placebo (treatment-policy estimand; Wadden TA et al. JAMA 2021 (STEP 3)).

What side effects were reported in STEP 3?

In STEP 3, discontinuation because of adverse events was 5.9% on 2.4 mg, against 2.9% on placebo. The most frequently reported adverse events were gastrointestinal adverse events in 82.8% on 2.4 mg against 63.2% on placebo, nausea in 58.2% on 2.4 mg against 22.1% on placebo, constipation in 36.9% on 2.4 mg against 24.5% on placebo and diarrhoea in 36.1% on 2.4 mg against 22.1% on placebo.