What the STEP 1 trial found about semaglutide and weight loss

Why this study matters

STEP 1 is the main trial behind the use of semaglutide (Wegovy, Ozempic) at the 2.4 mg dose for weight management. It answered a simple question: does a weekly injection of semaglutide, added to lifestyle support, help adults without diabetes lose weight over about 16 months? Many Canadian readers will have heard the headline numbers from this trial. This page explains where those numbers come from and what they do and do not mean.

Who was in the study

The trial enrolled 1961 adults. Everyone had a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher plus at least one weight-related health condition. BMI is a number that compares weight with height. No one in the trial had diabetes. The trial ran for 68 weeks. The published summary we reviewed does not report the age range of participants or the countries where the trial was run.

What the researchers did

This was a randomized, double-blind trial. Randomized means a computer decided by chance who got the medicine and who got the placebo. Double-blind means neither the participants nor the study staff knew who was getting which. A placebo is an injection that looks the same but has no active medicine.

For every two people assigned to semaglutide, one was assigned to placebo. The semaglutide group received a once-weekly injection under the skin at a dose of 2.4 mg. Both groups also received a lifestyle intervention, which means support with diet and physical activity.

The main results were the percentage change in body weight and the share of people who lost at least 5% of their starting weight, both measured at week 68. The researchers used what is called a primary estimand. An estimand is a precise description of what the trial is measuring. In STEP 1, it counted results regardless of whether someone stopped treatment or needed extra help.

What they found

At week 68, average body weight had changed by -14.9% in the semaglutide group and by -2.4% in the placebo group (R32-C01). The difference between the groups was -12.4 percentage points, with a 95% confidence interval of -13.4 to -11.5. A confidence interval is the range in which the true difference is likely to sit. Because the whole range is well below zero, the benefit was clear.

In kilograms, the semaglutide group changed by -15.3 kg and the placebo group by -2.6 kg. The difference was -12.7 kg (95% CI -13.7 to -11.7).

People taking semaglutide also had bigger improvements in heart and metabolic risk factors, and reported a bigger gain in physical functioning, than people taking placebo. The summary we reviewed does not give the numbers for those outcomes.

Side effects and people who stopped

Nausea and diarrhea were the most common side effects with semaglutide. The authors describe them as usually short-lived, mild to moderate, and easing over time. More people stopped treatment because of gastrointestinal (stomach and bowel) events in the semaglutide group: 59 people (4.5%) compared with 5 people (0.8%) in the placebo group (R32-C02). The summary we reviewed does not report the overall rate of people who stopped for any reason, or the rate of stopping for all side effects combined.

What this study does not tell you

• Our summary is based on the abstract and extracted data, not the full paper.
• Both groups received lifestyle support, so the results show what semaglutide adds to that support, not what it does alone.
• This trial did not compare semaglutide with any other weight-management medicine. Results from different trials cannot be lined up against each other, because the people, settings and support differed.
• People with diabetes were excluded, so the results do not apply to them. STEP 2 looked at that group separately.
• The trial lasted 68 weeks. It does not show what happens after treatment stops. The STEP 1 extension and STEP 4 studied that question.
• The trial was funded by the company that makes semaglutide.

What it means in Canada

STEP 1 is the trial most often quoted when semaglutide for weight management is discussed. The numbers on this page come from a controlled research setting with regular study visits and lifestyle support, which may differ from everyday care. For how the medicine is used in Canada, see semaglutide in Canada. For questions about what provincial plans pay for, see public drug coverage by province. To look at care options, see compare services.

Related reading

Other studies in this library that bear on the same question.

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