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Trials

STEP 1: semaglutide 2.4 mg for obesity over 68 weeks

The main semaglutide weight trial. 1961 adults without diabetes, 68 weeks: about 15 percent weight loss on semaglutide 2.4 mg versus 2 percent on placebo.

2 min readUpdated September 4, 2026By FormBlends editorial team2 sourcesEducational, not medical advice

STEP 1: weight change by arm at 68 weeks

From the data
STEP 1: Semaglutide 2.4 mg changed body weight -14.9 percent at 68 weeks versus -2.4 percent on placebo.Horizontal bars for each arm of STEP 1. Semaglutide 2.4 mg: -14.9 percent; Placebo: -2.4 percent.Percent change in body weight (loss shown as bar length)0%-5%-10%-15%Semaglutide 2.4 mg-14.9%-12.5 points versus placeboPlacebo-2.4%
Mean percent change in body weight from baseline, 1,961 randomised. Difference labels subtract the placebo mean from each active arm's mean. Source: PubMed 33567185. Source: N Engl J Med 2021;384(11):989-1002, PubMed 33567185.

Watch, with the fact-check

Clinical Trial Finds Weight Loss Medication Reduces Heart Events

Cleveland Clinic · 1:01 · uploaded 2023

What it gets right. A one-minute Cleveland Clinic clip in which a SELECT investigator states the headline: a roughly 20 percent relative reduction in major cardiovascular events in people with prior cardiovascular disease and overweight or obesity without diabetes.

What it leaves out. The transcript says 'over 177,000 patients'; the trial enrolled 17,604. Relative risk only, no absolute numbers, no adverse-event discontinuation figure.

Watch on YouTube

Embedded from YouTube (privacy-enhanced player, loads on click); verified against YouTube's oEmbed record on 2026-09-04. Nothing is rehosted. The fact-check is the FormBlends editorial team's reading, not the channel's endorsement.

STEP 1 is the trial behind the Wegovy approval and the origin of the "about 15 percent" figure for semaglutide. Here is what its primary publication states.

What the trial asked

Whether once-weekly semaglutide 2.4 mg, added to lifestyle intervention, reduces body weight in adults with obesity or overweight who do not have diabetes.

Design

Double-blind, randomised 2:1 to semaglutide 2.4 mg or placebo, once weekly for 68 weeks, both with lifestyle intervention. The primary estimand assessed effects regardless of treatment discontinuation or rescue interventions, which is the treatment-policy approach. The paper defines an estimand in its own abstract as "a precise description of the treatment effect reflecting the objective of the clinical trial," which is a fair one-line summary.

Who was enrolled

1961 adults with a BMI of 30 or greater, or 27 or greater with at least one weight-related coexisting condition, without diabetes. The abstract does not state baseline weight or age, so they are not reported here.

Primary endpoint and result

Coprimary endpoints at week 68: percent change in body weight, and weight reduction of at least 5 percent.

ArmMean weight change at week 68Mean change in kg
Semaglutide 2.4 mg-14.9%-15.3 kg
Placebo-2.4%-2.6 kg

Estimated treatment difference: -12.4 percentage points (95% CI -13.4 to -11.5; P less than 0.001). In kilograms: -12.7 kg (95% CI -13.7 to -11.7).

Responder thresholds at week 68, semaglutide versus placebo:

ThresholdSemaglutidePlacebo
5% or more1047 (86.4%)182 (31.5%)
10% or more838 (69.1%)69 (12.0%)
15% or more612 (50.5%)28 (4.9%)

P less than 0.001 for all three comparisons of odds.

Key secondary results

The abstract states that semaglutide participants had greater improvement in cardiometabolic risk factors and a greater increase in participant-reported physical functioning than placebo. It does not give the values.

Adverse events and discontinuation

Nausea and diarrhoea were the most common adverse events with semaglutide, typically transient and mild to moderate, and subsided with time. More participants on semaglutide than on placebo discontinued treatment because of gastrointestinal events: 59 (4.5 percent) versus 5 (0.8 percent). The abstract does not give an all-cause discontinuation rate.

Funding and registration

Novo Nordisk. ClinicalTrials.gov NCT03548935.

What this trial does not show

  • It excluded people with diabetes. STEP 2 tested the same dose in that population and found a smaller effect.
  • It stops at week 68. Longer follow-up is in STEP 5 (104 weeks), and withdrawal is in STEP 4.
  • It did not compare semaglutide with any other drug. For that, see STEP 8 (liraglutide) and SURMOUNT-5 (tirzepatide).
  • It is not evidence about compounded semaglutide, which was not the product tested and is not FDA approved.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 33567185), fetched 4 September 2026. The FormBlends semaglutide complete guide covers dosing and practical questions; the projection calculator applies the STEP 1 arm average to a body weight.

Sources (2)

  1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med 2021;384(11):989-1002. PubMed 33567185 Accessed September 4, 2026.
  2. ClinicalTrials.gov NCT03548935 Accessed September 4, 2026.

Canonical URL: https://formblendsresearch.com/trials/step-1. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.