The main finding
In one sentence: After 20 weeks on semaglutide, people who kept taking it lost a further 7.9% of their body weight over the next 48 weeks, while people switched to a placebo regained 6.9%.
Group averages, not an individual prediction. A trial result describes what happened to a defined group over a defined time.
On this page
Why this study matters
Many people want to know whether weight loss from a medicine lasts after the medicine stops. STEP 4 was designed to answer exactly that question for semaglutide (Wegovy, Ozempic). It is one of the main trials that clinicians point to when they explain why obesity is treated as a long-term condition. For Canadian readers weighing the cost and commitment of an ongoing medicine, it is a key piece of evidence.
Who was in the study
The trial enrolled 902 adults with a body mass index, or BMI, of at least 30, or at least 27 with at least one weight-related health condition. BMI is a number that relates weight to height. People with diabetes were not included. It ran at 73 sites in 10 countries from June 2018 to March 2020.
After the first 20 weeks, 803 people (89.0%) had reached the full 2.4 mg weekly dose and went on to the randomized part of the trial. Their average age was 46 years, 79% were women, and their average body weight was 107.2 kg. The whole trial lasted 68 weeks.
What the researchers did
STEP 4 used a design called randomized withdrawal. Everyone started on weekly semaglutide injections. The dose was raised over 16 weeks and then held at 2.4 mg for 4 weeks. During this 20-week run-in, people lost an average of 10.6% of their body weight.
At week 20, the 803 people who had reached the full dose were randomized. Randomized means they were assigned by chance, with a two-to-one split. In total, 535 continued semaglutide and 268 were switched to a placebo, which is an injection that looks the same but has no medicine in it. Neither the participants nor the researchers knew who received which, a set-up called double-blind. Both groups continued a lifestyle program during the 48-week randomized period.
The main outcome was the percentage change in body weight from week 20 to week 68.
What they found
From week 20 to week 68, average body weight changed by -7.9% in the group that continued semaglutide and by +6.9% in the group switched to placebo (R32-C07). The difference between groups was -14.8 percentage points, with a 95% confidence interval of -16.0 to -13.5. A confidence interval is the range within which the true difference most likely sits.
Other measures also favoured continuing semaglutide over the placebo switch:
| Measure, week 20 to week 68 | Difference, semaglutide vs placebo (95% CI) |
|---|---|
| Body weight | -14.8 percentage points (-16.0 to -13.5) |
| Waist size | -9.7 cm (-10.9 to -8.5) |
| Systolic blood pressure | -3.9 mmHg (-5.8 to -2.0) |
| Physical functioning score (SF-36) | 2.5 points (1.6 to 3.3) |
Systolic blood pressure is the top number in a blood pressure reading. The SF-36 is a questionnaire about health and daily function.
Most people stayed in the trial: 787 (98.0%) completed it and 741 (92.3%) completed their assigned treatment.
Side effects and people who stopped
Stomach and bowel side effects were reported by 49.1% of people who continued semaglutide and 26.1% of people on placebo. Similar small numbers stopped treatment because of side effects: 2.4% with semaglutide and 2.2% with placebo. The published summary we reviewed does not report the overall number of people who stopped treatment in each group for any reason.
What this study does not tell you
- Only people who reached and tolerated the full 2.4 mg dose during the run-in were randomized. The results do not describe everyone who starts the medicine (R32-C08).
- The weight change is measured from week 20, not from the start. The 10.6% loss during run-in happened before anyone was randomized.
- Both groups kept getting lifestyle support, so the trial cannot show what happens when a person stops both the medicine and the support.
- People with diabetes were not included, and the randomized part lasted 48 weeks, so it does not show what happens over several years.
- Results from this trial should not be compared side by side with stopping trials of other medicines, because the designs and populations differ.
- We reviewed the abstract only, so details on funding and analysis methods were not checked.
What it means in Canada
STEP 4 is often cited in Canadian discussions about how long a weight-management medicine needs to be taken. It shows that, in this trial, the benefit continued while the medicine continued and reversed when it stopped. It does not describe how the medicine is used, prescribed or paid for in Canada. See semaglutide in Canada for the medicine itself, public drug coverage by province for cost questions, and compare services for care options.
Common questions
How much weight did people regain after stopping semaglutide in STEP 4?
People switched to placebo at week 20 gained back 6.9% of their body weight by week 68, while people who kept taking semaglutide lost a further 7.9%.
How long did STEP 4 last?
Everyone took semaglutide for 20 weeks, then was randomized to continue it or switch to placebo for 48 more weeks, for 68 weeks in total.
Did people in STEP 4 get lifestyle support?
Yes. Both groups continued a lifestyle program during the 48-week randomized period, so the difference between groups reflects the medicine.
Related reading
Other studies in this library that bear on the same question.
One year after stopping semaglutide: the STEP 1 extension
What happens to weight when tirzepatide is stopped: SURMOUNT-4
STEP 1: semaglutide for weight loss in adults
STEP 5: two years of semaglutide
One year after stopping liraglutide or exercise: S-LiTE
Source
Original paper: Domenica Rubino, STEP 4, JAMA, 2021. PubMed: https://pubmed.ncbi.nlm.nih.gov/33755728/. DOI: https://doi.org/10.1001/jama.2021.3224. Funding: The summary we reviewed does not state the funding source. How we summarized it: abstract and extracted data.
This page explains a published study. It is not medical advice and does not describe whether a medicine is right for you. Talk to your doctor, nurse practitioner or pharmacist about your own situation. Reviewed and signed by two pharmacists registered in British Columbia, 2026-09-18.
Evidence records behind this page
Each record is a row in the clinical evidence file, taken from the published paper named above. The caution column is the limit the researcher recorded for that number.
This table scrolls sideways.
| Record | What the paper reports | Type | Population | Caution | Source |
|---|---|---|---|---|---|
| R32-C07 | After a 20-week semaglutide run-in in STEP 4, participants continuing treatment lost a further 7.9% of their weight over 48 weeks, while those switched to placebo regained 6.9%; lifestyle support continued in both groups. | direct evidence | Adults with overweight/obesity without diabetes who reached semaglutide 2.4 mg after run-in | Enriched for participants who completed and tolerated run-in; randomized change starts at week 20; both arms continued lifestyle intervention; full text connector failed twice. | PubMed 33755728 |
| R32-C08 | STEP 4 randomized participants who had reached and tolerated the maintenance dose, so its withdrawal results do not represent everyone starting treatment. | direct evidence | Adults with overweight/obesity without diabetes who reached semaglutide 2.4 mg after run-in | Enriched for participants who completed and tolerated run-in; randomized change starts at week 20; both arms continued lifestyle intervention; full text connector failed twice. | PubMed 33755728 |