STEP 1: what the trial showed
In 1,961 adults with obesity but without diabetes, once-weekly semaglutide 2.4 mg plus lifestyle intervention produced a mean weight change of -14.9% at 68 weeks against -2.4% with placebo, a difference of 12.4 percentage points, with gastrointestinal effects the main adverse events.
Main cited publication: Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 2021. PMID 33567185. Results are summarized from the cited trial report and any companion publications listed below.
At a glance
| Design | Randomised, double-blind, placebo-controlled, 2:1 allocation, 68 weeks |
|---|---|
| Population | 1,961 adults with a BMI of 30 or more (or 27 or more with at least one weight-related condition), without diabetes |
| Intervention | Semaglutide 2.4 mg subcutaneously once weekly plus lifestyle intervention |
| Comparator | Placebo plus lifestyle intervention |
| Follow-up | 68 weeks |
| Registration | NCT03548935 |
| Funding | Novo Nordisk |
Primary outcome
Coprimary: percentage change in body weight, and proportion achieving at least 5% weight reduction, at week 68.
| Semaglutide 2.4 mg subcutaneously once weekly plus lifestyle intervention | Placebo plus lifestyle intervention | Effect |
|---|---|---|
| -14.9% mean weight change; 86.4% lost at least 5% | -2.4% mean weight change; 31.5% lost at least 5% | Estimated treatment difference -12.4 percentage points (95% CI -13.4 to -11.5), P<0.001 |
Key findings
- Weight reductions of 10% or more were achieved by 69.1% versus 12.0%, and of 15% or more by 50.5% versus 4.9%.
- In kilograms, the change was -15.3 kg with semaglutide versus -2.6 kg with placebo (difference -12.7 kg, 95% CI -13.7 to -11.7).
- Cardiometabolic risk factors and participant-reported physical functioning improved more with semaglutide.
Harms and safety
- Nausea and diarrhoea were the most common adverse events with semaglutide, typically transient and mild to moderate.
- Discontinuation because of gastrointestinal events was 4.5% with semaglutide versus 0.8% with placebo.
Limitations
- 68 weeks of treatment; the follow-on STEP 1 extension showed substantial weight regain after stopping, so the result describes continuous therapy.
- Participants were mostly women and predominantly white, and people with diabetes were excluded.
- Industry funded; lifestyle intervention was delivered in both arms, so the trial does not compare semaglutide with intensive lifestyle programmes alone.
Where it sits in guidelines
The STEP programme underpinned the EU marketing authorisation of semaglutide 2.4 mg (Wegovy) for weight management in January 2022. European obesity guidance treats it as an adjunct to lifestyle intervention in adults meeting BMI criteria.
CliniAtlas answers that use this trial
Written for healthcare professionals as an orientation to the primary publication, not as a substitute for reading it. For literature search, education, and professional evidence review only. Not for diagnosis, treatment selection, triage, monitoring, prognosis, or patient-specific clinical decision-making.