Stopping Tirzepatide: SURMOUNT-4 Weight Regain

What happens when tirzepatide is stopped? In the SURMOUNT-4 trial, participants who switched to placebo after 36 weeks regained an average of 14% of body weight over the next year. Participants who continued lost a further 5.5%. Weight effects depended on continued treatment.

This original FirstLabs editorial review was updated November 3, 2026. It is educational information, not medical advice, a dosing guide or a recommendation for personal use. FirstLabs catalogue materials are for laboratory research only, not human or veterinary use.

How SURMOUNT-4 was designed

Aronne and colleagues used a randomized withdrawal design. All participants received open-label tirzepatide for a 36-week lead-in. The 670 who completed it were then randomized to continue tirzepatide or switch to placebo for another 52 weeks, to week 88. Participants had a mean age of 48 and mean starting weight of 107.3 kg; 71% were women. People with diabetes were excluded.

Results

Lead-in (weeks 0–36): mean weight reduction of 20.9%.
Weeks 36–88: −5.5% with continued tirzepatide versus +14.0% after switching to placebo, a difference of 19.4 percentage points.
Kept at least 80% of lead-in loss: 89.5% of the continued group versus 16.6% of the placebo group.
Overall (weeks 0–88): −25.3% with continued tirzepatide versus −9.9% for those switched to placebo.

Gastrointestinal side effects, mostly mild to moderate, were more common with tirzepatide.

What this means

The authors concluded that withdrawing tirzepatide led to substantial weight regain, while continuing maintained and added to the initial reduction. This matches the pattern seen in other obesity-medicine withdrawal trials: these medicines act while they are taken, not as a permanent reset.

Because everyone first completed a 36-week lead-in, participants who stopped early for side effects or other reasons were not randomized. Results may look better than in an unselected group.

Stopping tirzepatide: frequently asked questions

Do people regain weight after stopping tirzepatide?

In SURMOUNT-4, those switched to placebo regained an average of 14% of body weight within a year.

Did any weight loss remain after stopping?

Yes. Across the full 88 weeks, the placebo-switch group was still 9.9% below starting weight on average.

Is this guidance for anyone's treatment?

No. Treatment decisions belong with a licensed clinician. FirstLabs material is for laboratory research only.

Laboratory documentation is a separate question

Evidence about tirzepatide in a clinical study does not establish that a FirstLabs vial is equivalent to the studied formulation. A certificate of analysis describes the submitted sample, not medical suitability or regulatory authorization. HPLC purity does not by itself establish quantity, sterility, endotoxin control or a match to current stock.

For laboratory records, verify exact identity and labelled size, analytical methods, measured quantity, sample identifiers and any available lot-to-stock documentation. A laboratory task ID is not automatically a manufacturing lot. Keep missing reports and adverse results visible rather than borrowing evidence from another size.

Related reading: Tirzepatide sleep apnea trials, heart failure trial and tirzepatide clinical evidence. See the Tirzepatide research catalogue for laboratory sizes. The cover is an illustrative scene, not trial data.

Read our COA verification checklist, published laboratory reports and Canadian regulation overview for these distinctions.

Primary sources and editorial scope

FirstLabs is a research-material supplier with a commercial interest in the compounds discussed, not a licensed pharmacy or an independent medical authority. Results belong to their original study populations, formulations and endpoints. No personal outcome, treatment protocol or authorization of catalogue products is implied.

Stopping vs Continuing Tirzepatide: SURMOUNT-4 Weight Regain Results