- One year after stopping semaglutide, people in the STEP 1 extension had regained about two-thirds of the weight they had lost.1
- In STEP 4 and SURMOUNT-4, people who kept taking the medicine kept losing weight, while those switched to placebo regained steadily.2,3
- These medicines work while they are taken. That is why they are generally treated as long-term treatment. Any change is a decision to make with your prescriber.
STEP 1 extension: one year off semaglutide
After the 68-week STEP 1 trial ended, a group of 327 participants were followed for another year with no medicine and no trial lifestyle programme.1
In the authors' words, people "regained two-thirds of their prior weight loss." Improvements in blood pressure, blood sugar and other markers also moved back towards where they started. Still, on average, people ended the two years about 5.6% lighter than when they began.
STEP 4: continue or switch to placebo
STEP 4 tested this head-on. All 803 participants took semaglutide for 20 weeks and lost an average of 10.6%. They were then randomly split: 535 continued semaglutide and 268 were switched to placebo without knowing it, for another 48 weeks.2
Those who continued lost a further 7.9%. Those switched to placebo gained 6.9% over the same period, a gap of 14.8 percentage points.
SURMOUNT-4: the same pattern with tirzepatide
SURMOUNT-4 did the same with tirzepatide. 670 participants took the medicine for 36 weeks and lost an average of 20.9%. Half then continued and half were switched to placebo for 52 weeks.3
| Continued tirzepatide | Switched to placebo | |
|---|---|---|
| Weight change, weeks 36–88 | −5.5% | +14.0% |
| Total change, weeks 0–88 | −25.3% | −9.9% |
As with semaglutide, people who stopped regained a large part of the weight, but on average they were still below their starting weight at the end of the trial.
Why the weight comes back
GLP-1 medicines reduce appetite while they are active in the body. When they stop, appetite and food intake tend to return towards where they were, while the body, now smaller, needs less energy than before. Obesity researchers increasingly describe it as a chronic condition, which is why these medicines are generally prescribed as ongoing treatment rather than a short course.
What this means in practice
- Talk before you stop. If cost, side effects or supply make you consider stopping or lowering a dose, discuss it with your prescriber first. There may be options you are not aware of.
- Habits still count. The trials show that regain is common, not that habits are pointless. Protein, strength training and regular weighing are the habits most often linked to keeping muscle and spotting change early. See the protein research.
- Track the trend, not the day. Day-to-day weight jumps around with water and salt. A weekly average shows the direction much more honestly.
- Averages are not destinies. In every trial some people regained little and some regained more than average.
Sources
- Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24:1553-1564. PubMed
- Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325:1414-1425. PubMed
- Aronne LJ, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331:38-48. PubMed
