The main finding
In one sentence: After 36 weeks on tirzepatide, people who kept taking it lost a further 5.5% of body weight over the next 52 weeks, while people switched to a placebo regained 14.0%.
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
People starting a weight-management medicine often ask whether they will need to stay on it. SURMOUNT-4 was built to answer that question for tirzepatide (Zepbound, Mounjaro). It took people who had already lost weight on the medicine and, by chance, either kept them on it or switched them to a placebo. The result helps explain why clinicians describe these medicines as long-term treatments rather than short courses.
Who was in the study
The trial enrolled 783 adults with a body mass index, or BMI, of 30 or more, or 27 or more with a weight-related health condition. BMI is a number that relates weight to height. People with diabetes were not included. It ran at 70 sites in 4 countries.
Of those 783, 670 completed the 36-week lead-in and were randomized. Their average age was 48 years, 71% were women, and their average weight was 107.3 kg. The whole trial lasted 88 weeks.
What the researchers did
For the first 36 weeks, everyone received weekly tirzepatide injections at their maximum tolerated dose of 10 or 15 mg. This part was open-label, meaning everyone knew what they were taking. Diet and physical activity support were part of the trial.
At week 36, the 670 people still in the trial were randomized, meaning assigned by chance, in a one-to-one split. In total, 335 continued tirzepatide and 335 were switched to a placebo, an injection that looks the same but has no medicine in it. This 52-week period was double-blind, so neither participants nor researchers knew who received which.
The main outcome was the percentage change in weight from week 36, the point of randomization, to week 88.
What they found
During the 36-week lead-in, people lost an average of 20.9% of their body weight.
From week 36 to week 88, average weight changed by -5.5% in the group that continued tirzepatide and by +14.0% in the group switched to placebo (R32-C50). The difference was -19.4 percentage points, with a 95% confidence interval of -21.2 to -17.7. A confidence interval is the range within which the true difference most likely sits.
A key secondary outcome looked at how many people held on to their weight loss. At week 88, 300 people (89.5%) still taking tirzepatide had kept at least 80% of the weight they lost during the lead-in, compared with 16.6% of people switched to placebo (R32-C51).
| Measure | Continued tirzepatide | Switched to placebo |
|---|---|---|
| Weight change, week 36 to 88 | -5.5% | +14.0% |
| Kept at least 80% of lead-in weight loss at week 88 | 89.5% | 16.6% |
| Total weight change, week 0 to 88 | -25.3% | -9.9% |
Over the whole 88 weeks, from the very start, weight fell by 25.3% with continued tirzepatide and 9.9% with the placebo switch.
Side effects and people who stopped
The most common side effects were stomach and bowel symptoms, mostly mild to moderate, and these were more common with tirzepatide than with placebo. The published summary we reviewed does not report the number of people in each group who stopped treatment, or who stopped because of side effects.
What this study does not tell you
- Only people who completed 36 weeks of tirzepatide were randomized. The result describes people who had already responded to and tolerated the medicine, not everyone who starts it.
- It does not estimate the benefit of starting the medicine in a general group of patients. SURMOUNT-1 answers that question.
- People with diabetes were not included, and the randomized period lasted 52 weeks, so it does not show what happens over several years off treatment.
- Results should not be compared side by side with stopping trials of other medicines, because the lead-in length, doses and populations differ.
- We reviewed the abstract only, so the funding source and analysis methods were not checked.
What it means in Canada
For Canadian readers, SURMOUNT-4 shows that, in this trial, weight loss from tirzepatide was maintained while the medicine continued and largely reversed within a year of switching to placebo. It does not describe how the medicine is prescribed or paid for here. See tirzepatide in Canada for the medicine, public drug coverage by province for cost questions, and compare services for care options.
Common questions
How much weight came back after stopping tirzepatide in SURMOUNT-4?
People switched to placebo at week 36 regained 14.0% of body weight by week 88, while people who continued tirzepatide lost a further 5.5%.
How many people kept most of their weight loss in SURMOUNT-4?
At week 88, 89.5% of people still taking tirzepatide had kept at least 80% of the weight they lost in the first 36 weeks, compared with 16.6% of people switched to placebo.
How long was the SURMOUNT-4 trial?
It had a 36-week open-label lead-in on tirzepatide followed by a 52-week randomized period, for 88 weeks in total.
Related reading
Other studies in this library that bear on the same question.
What happens to weight when semaglutide is stopped: STEP 4
Tirzepatide for weight loss in adults without diabetes: SURMOUNT-1
Switching from an injection to oral orforglipron: ATTAIN-MAINTAIN
One year after stopping semaglutide: the STEP 1 extension
Tirzepatide versus semaglutide head to head: SURMOUNT-5
Source
Original paper: Louis J Aronne, SURMOUNT-4, JAMA, 2024. PubMed: https://pubmed.ncbi.nlm.nih.gov/38078870/. DOI: https://doi.org/10.1001/jama.2023.24945. 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-C50 | After the 36-week tirzepatide lead-in in SURMOUNT-4, weight fell a further 5.5% over 52 weeks among participants continuing treatment; weight increased 14.0% from the week-36 level among those switched to placebo. | direct evidence | Adults with obesity or overweight plus complication, without diabetes, completing tirzepatide lead-in | Enriched withdrawal design after 36 weeks of treatment; does not estimate starting-treatment benefit in all patients. Full-text connector failed twice; abstract-only. | PubMed 38078870 |
| R32-C51 | At week 88, 89.5% of those continuing tirzepatide maintained at least 80% of their initial loss, compared with 16.6% after switching to placebo. | direct evidence | Adults with obesity or overweight plus complication, without diabetes, completing tirzepatide lead-in | Enriched withdrawal design after 36 weeks of treatment; does not estimate starting-treatment benefit in all patients. Full-text connector failed twice; abstract-only. | PubMed 38078870 |