---
title: "STEP 4: Semaglutide Phase 3 Results | Primara Labs"
url: https://www.primaralabs.com/research/trials/step-4
source: Primara Labs, markdown mirror of the HTML page
---

# STEP 4

In STEP 4, a phase 3 trial of semaglutide in adults with BMI of at least 30 (or 27 or greater with at least 1 weight-related comorbidity) without diabetes, who reached the 2.4 mg maintenance dose during a 20-week run-in (n=803), mean body weight changed by -7.9% on continued 2.4 mg, weeks 20 to 68 over 68 weeks, against +6.9% on switched to placebo (treatment-policy estimand; Rubino D et al. JAMA 2021 (STEP 4)).

Primara Labs sells some of the compounds covered here. Every figure on this page links to its source and the date it was checked.

Updated 24 September 2026

Semaglutide Explained: STEP, SUSTAIN and SELECT Trials (Philippines)2:07·[Transcript and chapters](https://www.primaralabs.com/videos/semaglutide)

## Results

Mean percent change in body weight by arm, as each source reports it. Navy bars are the trial arms, grey bars the comparator. Bars from different trials are not a head-to-head comparison: populations, durations and estimands differ.

## Side effects reported

In STEP 4, discontinuation because of adverse events was 2.4% on continued 2.4 mg, weeks 20 to 68, against 2.2% on switched to placebo. The most frequently reported adverse events were gastrointestinal adverse events in 41.9% on continued 2.4 mg, weeks 20 to 68 against 26.1% on switched to placebo, diarrhoea in 14.4% on continued 2.4 mg, weeks 20 to 68 against 7.1% on switched to placebo, nausea in 14.0% on continued 2.4 mg, weeks 20 to 68 against 4.9% on switched to placebo and constipation in 11.6% on continued 2.4 mg, weeks 20 to 68 against 6.3% on switched to placebo.

| Event | Continued 2.4 mg, weeks 20 to 68 | Switched to placebo |
| --- | --- | --- |
| Discontinuation for adverse events | 2.4% | 2.2% |
| Gastrointestinal adverse events | 41.9% | 26.1% |
| Diarrhoea | 14.4% | 7.1% |
| Nausea | 14.0% | 4.9% |
| Constipation | 11.6% | 6.3% |
| Vomiting | 10.3% | 3.0% |

Design

## Trial design and sources

Compound

Semaglutide

Phase

3

Population

Adults with BMI of at least 30 (or 27 or greater with at least 1 weight-related comorbidity) without diabetes, who reached the 2.4 mg maintenance dose during a 20-week run-in

Participants randomised

803

Duration

68 weeks

Primary endpoint

Percent change in body weight from week 20 to week 68

Estimand

treatment-policy

Read out

1 April 2021

Withdrawal design: all participants took semaglutide for a 20-week run-in, then were randomised to continue or switch to placebo. The switch-to-placebo arm regained weight. The abstract gives gastrointestinal events as 49.1%; the results text and Table 3 give 41.9%.

-   Rubino D et al. JAMA 2021 (STEP 4) [open](https://doi.org/10.1001/jama.2021.3224) · checked 23 September 2026
-   ClinicalTrials.gov NCT03548987 [open](https://clinicaltrials.gov/study/NCT03548987) · checked 23 September 2026
-   Registry: NCT03548987

Questions

## STEP 4, answered

### What did STEP 4 find?

In STEP 4, a phase 3 trial of semaglutide in adults with BMI of at least 30 (or 27 or greater with at least 1 weight-related comorbidity) without diabetes, who reached the 2.4 mg maintenance dose during a 20-week run-in (n=803), mean body weight changed by -7.9% on continued 2.4 mg, weeks 20 to 68 over 68 weeks, against +6.9% on switched to placebo (treatment-policy estimand; Rubino D et al. JAMA 2021 (STEP 4)).

### What side effects were reported in STEP 4?

In STEP 4, discontinuation because of adverse events was 2.4% on continued 2.4 mg, weeks 20 to 68, against 2.2% on switched to placebo. The most frequently reported adverse events were gastrointestinal adverse events in 41.9% on continued 2.4 mg, weeks 20 to 68 against 26.1% on switched to placebo, diarrhoea in 14.4% on continued 2.4 mg, weeks 20 to 68 against 7.1% on switched to placebo, nausea in 14.0% on continued 2.4 mg, weeks 20 to 68 against 4.9% on switched to placebo and constipation in 11.6% on continued 2.4 mg, weeks 20 to 68 against 6.3% on switched to placebo.

Related

## More on semaglutide

-   [STEP 1](https://www.primaralabs.com/research/trials/step-1)
-   [STEP 2](https://www.primaralabs.com/research/trials/step-2)
-   [STEP 3](https://www.primaralabs.com/research/trials/step-3)
-   [STEP 5](https://www.primaralabs.com/research/trials/step-5)
-   [STEP 8](https://www.primaralabs.com/research/trials/step-8)
-   [SELECT](https://www.primaralabs.com/research/trials/select)
-   [SURMOUNT-5](https://www.primaralabs.com/research/trials/surmount-5)
-   [Evidence Map: Semaglutide](https://www.primaralabs.com/research/evidence#semaglutide)
-   [Semaglutide 15mg](https://www.primaralabs.com/marketplace/semaglutide-15mg)