Evidence section
What happens when weight-management medicines are stopped
Two pharmacists registered and practising in British Columbia read this page against the study pages and papers it lists and signed it. Their names are withheld from the site and held on file; their registration is confirmed on request.
Several trials deliberately stopped the medicine, or switched people to placebo, and kept measuring. They are among the most important studies for anyone deciding about long-term treatment, because they show what tends to happen to weight and to blood pressure, blood sugar and cholesterol after the medicine ends. This hub collects them in one place. The pattern across studies is consistent, but the amounts differ by medicine, dose and follow-up length.
What these studies show together
In every study here, weight went back up after the medicine was stopped or replaced with a placebo. In the trials that randomly kept one group on treatment, that group kept losing weight or held most of its loss while the other group regained. How much came back differed by medicine, dose, how long people had been treated and how long they were followed, so the five studies answer the same question in different ways rather than adding up to one number.
The studies side by side
| Study | Medicine | Who was studied | Treated before the stop | Followed after the stop | Support after the stop | Main weight result, as reported |
|---|---|---|---|---|---|---|
| STEP 4 | Semaglutide 2.4 mg | 803 adults without diabetes who reached the full dose | 20 weeks | 48 weeks, randomized to continue or switch to placebo | Lifestyle program continued in both groups | Switched to placebo: +6.9%. Continued: -7.9% (from week 20) |
| STEP 1 extension | Semaglutide 2.4 mg or placebo | 327 adults without diabetes who completed 68 weeks (a selected subset) | 68 weeks | 52 weeks, everyone off treatment | None: medicine and lifestyle support both stopped | Regained 11.6 of the 17.3 percentage points lost; still 5.6% below the starting weight |
| SURMOUNT-4 | Tirzepatide 10 or 15 mg | 670 adults without diabetes who completed a 36-week lead-in | 36 weeks | 52 weeks, randomized to continue or switch to placebo | Diet and activity support were part of the trial | Switched to placebo: +14.0%. Continued: -5.5% (from week 36) |
| S-LiTE | Liraglutide 3.0 mg, supervised exercise, both, or placebo | Adults aged 18 to 65 in Copenhagen after a low-calorie diet; 109 of 195 attended the follow-up | 52 weeks | 52 weeks, everyone off treatment | None | Estimated regain: 9.6 kg after liraglutide alone, 7.1 kg after both, 3.6 kg after exercise alone |
| ATTAIN-MAINTAIN | Switch to orforglipron pill or placebo | 376 adults without type 2 diabetes who completed SURMOUNT-5 | 72 weeks of tirzepatide or semaglutide | 52 weeks, randomized | Rescue orforglipron allowed from week 24 | Share of earlier loss kept: 74.7% vs 49.2% after tirzepatide; 79.3% vs 37.6% after semaglutide |
What is consistent
Regain followed stopping in every placebo or off-treatment group: in STEP 4, the STEP 1 extension, SURMOUNT-4, S-LiTE and both placebo groups of ATTAIN-MAINTAIN. In the two trials that randomized people to continue or stop the same medicine, STEP 4 and SURMOUNT-4, the difference between the groups was large and statistically clear.
Within the follow-up periods studied, regain was partial on average rather than complete. One year after stopping in the STEP 1 extension, the semaglutide group was still 5.6% below its starting weight. At the end of SURMOUNT-4, the group switched to placebo was 9.9% below its starting weight. Where the studies measured blood pressure and other risk factors, the improvements moved back toward their starting values after stopping (STEP 1 extension) or were larger in the group that continued (STEP 4).
What differs, and why the numbers should not be lined up
The studies stopped treatment at different points (after 20, 36, 52, 68 or 72 weeks) and measured the result in different ways: STEP 4 and SURMOUNT-4 from the day of randomization, the STEP 1 extension from the start of the original trial, S-LiTE in kilograms, and ATTAIN-MAINTAIN as the share of earlier loss that was kept.
STEP 4 and SURMOUNT-4 randomized only people who had already reached and tolerated the full dose, so they describe people who responded, not everyone who starts a medicine. The STEP 1 extension followed a selected subset of completers, and more than two in five people randomized in S-LiTE did not attend its follow-up visit.
For these reasons, the larger regain after stopping tirzepatide in SURMOUNT-4 than after stopping semaglutide in STEP 4 is not a comparison of the two medicines. The lead-in length, doses and the amount of weight lost before stopping all differed.
What these studies cannot tell you
None of them tested reducing the dose gradually or any particular way of stopping, and none followed people for more than one year after stopping. STEP 4, the STEP 1 extension and SURMOUNT-4 did not include people with diabetes. The support people received after stopping also differed: in STEP 4 the lifestyle program continued, while in the STEP 1 extension and S-LiTE all treatment ended, so the studies cannot separate the effect of stopping the medicine from the effect of stopping the support. Orforglipron, studied in ATTAIN-MAINTAIN, is not approved in Canada.
Decisions about continuing, changing or stopping a medicine belong with the prescriber, who knows the person's history. For the medicines themselves and how they are paid for in Canada, see semaglutide in Canada, tirzepatide in Canada and public drug coverage by province.
This summary draws only on the study pages listed below and adds no figures that are not on them. Written 2026-09-23; reviewed by two pharmacists registered in British Columbia, 2026-09-23.
Studies in this section (5)
What happens to weight when semaglutide is stopped: STEP 4
STEP 4 tested what happens when semaglutide is switched to placebo after 20 weeks. Plain-language results on weight regain for Canadian readers.
One year after stopping semaglutide: the STEP 1 extension
One year after STEP 1 ended, people who had taken semaglutide regained about two-thirds of their lost weight. A plain-language summary with Canadian sites.
One year after stopping liraglutide or exercise: S-LiTE
S-LiTE followed adults for a year after stopping liraglutide, supervised exercise or both. Plain-language results on weight regain for Canadian readers.
What happens to weight when tirzepatide is stopped: SURMOUNT-4
SURMOUNT-4 switched half of its participants from tirzepatide to placebo after 36 weeks. Plain-language results on weight regain for Canadian readers.
Switching from an injection to oral orforglipron: ATTAIN-MAINTAIN
ATTAIN-MAINTAIN tested a daily orforglipron pill after stopping tirzepatide or semaglutide. Research only: orforglipron is not approved in Canada.
Other evidence sections
How to read these pages
Every page in this section explains one published study. The numbers are reported as the researchers published them, with a link to the paper on PubMed. Pages say what a study cannot tell you and never rank one medicine against another. They are education, not medical advice. For how a medicine is used and paid for in Canada, see medicines, public drug coverage by province and compare services.
Reviewed and signed by two pharmacists registered in British Columbia, 2026-09-23.