STEP 5: what two years of semaglutide did to body weight

Why this study matters

Most of the first semaglutide (Wegovy, Ozempic) weight trials ran for 68 weeks, about 16 months. STEP 5 is the trial that answers a longer question: what happens if people keep taking the medicine for two full years? For Canadian readers thinking about long-term treatment, this is the randomized evidence on whether weight loss holds up, and what side effects look like, over 104 weeks.

Who was in the study

STEP 5 enrolled 304 adults. All had obesity, or overweight with at least one weight-related health condition, and none had diabetes. Half (152) were assigned to semaglutide and half (152) to placebo. People were enrolled between 5 October 2018 and 1 February 2019.

Most participants were female (236 people, 77.6%) and white (283 people, 93.1%). The mean age was 47.3 years. The mean body mass index (BMI) was 38.5. BMI is a number that compares weight with height, in kilograms per metre squared. Mean body weight at the start was 106.0 kg. By the end, 92.8% of participants attended the final safety visit.

The trial had Canadian authors or sites, according to the extracted data. The summary we reviewed does not name the sites.

What the researchers did

This was a randomized, placebo-controlled trial. Randomized means chance decided who got which treatment. Placebo means an inactive injection that looks like the real one, so neither group knew what they were getting.

One group injected semaglutide 2.4 mg under the skin once a week. The other injected placebo once a week. Both groups also received a behavioural intervention, meaning regular support with food and activity. The trial lasted 104 weeks.

The two main outcomes were the percentage change in body weight and the share of people who lost at least 5% of their starting weight, both at week 104. The researchers counted everyone who was randomized, whether or not they stayed on the medicine or used other weight treatments. This approach is called a treatment-policy estimand. An estimand is simply a precise statement of what question the numbers are meant to answer. Here, the question was "what happens to people assigned to this treatment", not "what happens to people who take every dose".

What they found

At week 104, mean body weight had changed by -15.2% in the semaglutide group and -2.6% in the placebo group (R32-C09). The estimated difference was -12.6 percentage points. The 95% confidence interval was -15.3 to -9.8. A confidence interval is the range of values the true difference is likely to fall in; if the whole range is below zero, the medicine group lost more weight than placebo.

Both results were highly unlikely to be due to chance (P less than 0.0001).

Side effects and people who stopped

Stomach and gut side effects, such as nausea, were reported by 82.2% of people on semaglutide and 53.9% on placebo. Most were mild to moderate.

Adverse events led to stopping trial treatment in 5.9% of the semaglutide group and 4.6% of the placebo group (R32-C10). The summary we reviewed does not report the total share of people who stopped treatment for any reason.

What this study does not tell you

• It was small for a two-year trial, with 152 people per group. Rare side effects cannot be measured in a trial this size.
• Participants were 77.6% female and 93.1% white, so the results may not apply equally to everyone.
• Both groups received behavioural support. The results show what semaglutide added on top of that support, not what the medicine does alone.
• No one in this trial had diabetes. See the STEP 2 page for results in people with type 2 diabetes.
• The trial measured weight, not heart attacks, strokes or other long-term health events.
• It does not tell you what happens after the medicine is stopped. See the STEP 4 and STEP 1 extension pages for that.
• Weight change in STEP 5 cannot be lined up against other trials of other medicines, because the people, support and time frames differ.

What it means in Canada

STEP 5 is the main randomized evidence that weekly semaglutide 2.4 mg kept weight off over two years while people stayed on it, with lifestyle support. It does not say what treatment costs or who qualifies. For that, see semaglutide in Canada and public drug coverage by province. To see how different care options are set up, see compare services.

Related reading

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

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