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Semaglutide · Phase 3b · Completed

STEP 8

In STEP 8, a phase 3b trial of semaglutide in US adults with BMI of 30 or greater, or 27 or greater with 1 or more weight-related comorbidities, without diabetes (n=338), mean body weight fell 15.8% on semaglutide 2.4 mg and 6.4% on liraglutide 3.0 mg over 68 weeks, against 1.9% on placebo (pooled) (treatment-policy estimand; Rubino DM et al. JAMA 2022 (STEP 8)).

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Results

STEP 8: mean percent change in body weight by armSTEP 8 treatment-policy estimandSemaglutide 2.4 mg-15.8%Liraglutide 3.0 mg-6.4%Placebo (pooled)-1.9%
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 8, discontinuation because of adverse events was 3.2% on semaglutide 2.4 mg and 12.6% on liraglutide 3.0 mg, against 3.5% on placebo (pooled). The most frequently reported adverse events were gastrointestinal disorders in 84.1% on semaglutide 2.4 mg and 82.7% on liraglutide 3.0 mg against 55.3% on placebo (pooled), nausea in 61.1% on semaglutide 2.4 mg and 59.1% on liraglutide 3.0 mg against 22.4% on placebo (pooled), constipation in 38.9% on semaglutide 2.4 mg and 31.5% on liraglutide 3.0 mg against 23.5% on placebo (pooled) and diarrhoea in 27.8% on semaglutide 2.4 mg and 18.1% on liraglutide 3.0 mg against 25.9% on placebo (pooled).

EventSemaglutide 2.4 mgLiraglutide 3.0 mgPlacebo (pooled)
Discontinuation for adverse events3.2%12.6%3.5%
Gastrointestinal disorders84.1%82.7%55.3%
Nausea61.1%59.1%22.4%
Constipation38.9%31.5%23.5%
Diarrhoea27.8%18.1%25.9%
Vomiting25.4%20.5%5.9%

Design

Trial design and sources

Compound
Semaglutide
Phase
3b
Population
US adults with BMI of 30 or greater, or 27 or greater with 1 or more weight-related comorbidities, without diabetes
Participants randomised
338
Duration
68 weeks
Primary endpoint
Percentage change in body weight, semaglutide vs liraglutide at week 68
Estimand
treatment-policy
Read out
1 January 2022

Semaglutide against liraglutide was open-label; each was blinded against its own placebo, pooled.

  • Rubino DM et al. JAMA 2022 (STEP 8) open · checked 23 September 2026
  • ClinicalTrials.gov NCT04074161 open · checked 23 September 2026
  • Registry: NCT04074161

Questions

STEP 8, answered

What did STEP 8 find?

In STEP 8, a phase 3b trial of semaglutide in US adults with BMI of 30 or greater, or 27 or greater with 1 or more weight-related comorbidities, without diabetes (n=338), mean body weight fell 15.8% on semaglutide 2.4 mg and 6.4% on liraglutide 3.0 mg over 68 weeks, against 1.9% on placebo (pooled) (treatment-policy estimand; Rubino DM et al. JAMA 2022 (STEP 8)).

What side effects were reported in STEP 8?

In STEP 8, discontinuation because of adverse events was 3.2% on semaglutide 2.4 mg and 12.6% on liraglutide 3.0 mg, against 3.5% on placebo (pooled). The most frequently reported adverse events were gastrointestinal disorders in 84.1% on semaglutide 2.4 mg and 82.7% on liraglutide 3.0 mg against 55.3% on placebo (pooled), nausea in 61.1% on semaglutide 2.4 mg and 59.1% on liraglutide 3.0 mg against 22.4% on placebo (pooled), constipation in 38.9% on semaglutide 2.4 mg and 31.5% on liraglutide 3.0 mg against 23.5% on placebo (pooled) and diarrhoea in 27.8% on semaglutide 2.4 mg and 18.1% on liraglutide 3.0 mg against 25.9% on placebo (pooled).