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Semaglutide · Phase 3 · Completed

STEP 5

In STEP 5, a phase 3 trial of semaglutide in adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes (n=304), mean body weight fell 15.2% on 2.4 mg over 104 weeks, against 2.6% on placebo (treatment-policy estimand; Garvey WT et al. Nat Med 2022 (STEP 5)).

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Results

STEP 5: mean percent change in body weight by armSTEP 5 treatment-policy estimand2.4 mg-15.2%Placebo-2.6%
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 5, discontinuation because of adverse events was 5.9% on 2.4 mg, against 4.6% on placebo. The most frequently reported adverse events were gastrointestinal adverse events in 82.2% on 2.4 mg against 53.9% on placebo, nausea in 53.3% on 2.4 mg against 21.7% on placebo, diarrhoea in 34.9% on 2.4 mg against 23.7% on placebo and constipation in 30.9% on 2.4 mg against 11.2% on placebo.

Event2.4 mgPlacebo
Discontinuation for adverse events5.9%4.6%
Gastrointestinal adverse events82.2%53.9%
Nausea53.3%21.7%
Diarrhoea34.9%23.7%
Constipation30.9%11.2%
Vomiting30.3%4.6%

Design

Trial design and sources

Compound
Semaglutide
Phase
3
Population
Adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes
Participants randomised
304
Duration
104 weeks
Primary endpoint
Co-primary: percentage change in body weight and achievement of weight loss of 5% or more at week 104
Estimand
treatment-policy
Read out
10 October 2022
  • Garvey WT et al. Nat Med 2022 (STEP 5) open · checked 23 September 2026
  • ClinicalTrials.gov NCT03693430 open · checked 23 September 2026
  • Registry: NCT03693430

Questions

STEP 5, answered

What did STEP 5 find?

In STEP 5, a phase 3 trial of semaglutide in adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes (n=304), mean body weight fell 15.2% on 2.4 mg over 104 weeks, against 2.6% on placebo (treatment-policy estimand; Garvey WT et al. Nat Med 2022 (STEP 5)).

What side effects were reported in STEP 5?

In STEP 5, discontinuation because of adverse events was 5.9% on 2.4 mg, against 4.6% on placebo. The most frequently reported adverse events were gastrointestinal adverse events in 82.2% on 2.4 mg against 53.9% on placebo, nausea in 53.3% on 2.4 mg against 21.7% on placebo, diarrhoea in 34.9% on 2.4 mg against 23.7% on placebo and constipation in 30.9% on 2.4 mg against 11.2% on placebo.