Weight regain after semaglutide: what two withdrawal studies tell us

The question

Weight regain after stopping semaglutide was substantial on average in two major studies. That does not mean every person regained everything, or that one percentage can predict an individual's future. The detail that makes the evidence useful is what happened after treatment ended—and what the researchers compared it with.

Two frequently cited reports, the STEP 1 extension and STEP 4, approached that question differently. Reading them together helps separate an observed pattern from a direct continuation-versus-withdrawal comparison.

STEP 1: a year after treatment and support ended

The STEP 1 extension followed a subset of adults without diabetes after the original trial. Its analysis included 327 participants. At week 68, study medication and the structured lifestyle intervention stopped. Over the following 52 weeks, the former semaglutide group regained an average 11.6 percentage points of body weight after an earlier 17.3% average loss. The reported net loss at week 120 was 5.6% from baseline. This was an exploratory observational extension, not a new randomization to stopping versus continuing. Original extension report.

The often-repeated “two-thirds regained” description refers to the share of the earlier loss regained on average. It does not mean two-thirds of participants regained all their weight. Those are different statements with different denominators.

For a separate, hypothetical arithmetic example, imagine a starting weight of 200 pounds and a 15% loss: 30 pounds. Regaining two-thirds of that loss would mean regaining 20 pounds, leaving the person 10 pounds below the starting weight. This is an explanation of the fraction, not a reconstruction of an individual trial participant or a forecast.

STEP 4: continuation versus switching to placebo

STEP 4 first gave participants semaglutide during a 20-week run-in. It then randomized 803 eligible participants who reached the maintenance regimen to continue semaglutide or switch to placebo for another 48 weeks. Both groups continued lifestyle intervention. From randomization onward, average weight changed by −7.9% with continued semaglutide and +6.9% after the switch. Gastrointestinal events were more frequent in the continuation group. Original randomized withdrawal trial.

This design provides a more direct treatment comparison. Its boundary is equally relevant: the randomized group had already completed the run-in. It does not represent everyone who might begin treatment, including those unable to reach that stage.

The percentages also start at a different point on the calendar. STEP 4's headline comparison begins at randomization, after initial treatment. Do not place it beside a baseline-to-follow-up percentage and assume the two numbers measure the same interval.

What the comparison adds

Stopping structured support in one study makes that study less able to isolate medication withdrawal on its own. Maintaining support in the other helps address that uncertainty. This is why reading the design can be more informative than collecting additional headlines with the same large number.

Neither report should become a judgment about motivation. A study measures an outcome under specified conditions; it does not measure someone's character. It also cannot tell an individual reader which treatment plan, if any, is appropriate for them.

Both trials were funded by Novo Nordisk. The STEP 1 registry record provides a separate record of the original study. Sponsor funding should be visible, alongside the design and limitations, rather than silently omitted or used as a reason to dismiss the results without reading them.

Keep the studied formulation in view

These findings concern the studied injectable semaglutide regimen. They are not withdrawal results for every semaglutide formulation or every product sold under the compound's name. FDA's March 2026 announcement of a higher-dose Wegovy approval illustrates why an older study should not be treated as an all-purpose description of the current product landscape. FDA announcement.

An approved finished medicine and a research-material listing are different products. Our tirzepatide–semaglutide comparison explains another reason to keep trial populations and endpoints attached to the result.

Questions to take into a treatment discussion

Rather than treating a group average as a personal deadline, ask what follow-up would look like if treatment changed: which outcomes would be monitored, what support would continue, and when the plan would be reassessed. Those questions leave room for medical history, tolerability and access—details a trial average cannot supply. Decisions about stopping or changing prescribed treatment belong with the prescribing clinician.