Research
SURMOUNT-4: the tirzepatide withdrawal trial
SURMOUNT-4 (NCT04660643) is the tirzepatide maintenance/withdrawal trial: after a 36-week open-label lead-in, continuing tirzepatide maintained weight
SURMOUNT-4 (NCT04660643) is the tirzepatide maintenance/withdrawal trial: after a 36-week open-label lead-in, continuing tirzepatide maintained weight loss while switching to placebo led to significant regain over the following 52 weeks. It mirrors STEP 4's finding for the dual agonist.
What the trials establish
SURMOUNT-4 used a 36-week lead-in on maximum tolerated tirzepatide (10 or 15 mg), then randomized participants to continue or switch to placebo for 52 weeks. Those who continued preserved and modestly extended their loss; those on placebo regained a large portion.
Together with STEP 4, it establishes that the withdrawal-regain pattern is a class characteristic, not a molecule-specific quirk. The physiology that drives loss also drives regain when the drug is removed.
SURMOUNT-4's identifiers are verified (JAMA 2024; DOI and PMID below). It is the empirical backbone of the maintenance discussion for tirzepatide.
| Trial | Population | N | Result | Citation | Identifiers |
|---|---|---|---|---|---|
| SURMOUNT-1 | Adults with obesity, without diabetes | 2,539 | Up to about -20.9% at 15 mg vs -3.1% placebo | Jastreboff AM, et al. N Engl J Med 2022;387(3):205-216 | NCT04184622 · PMID 35658024 · DOI |
| SURMOUNT-4 | Adults with obesity after lead-in | 670 | Continued treatment maintained loss; withdrawal led to regain | Aronne LJ, et al. JAMA 2024;331(1):38-48 | NCT04660643 · PMID 38078870 · DOI |
Identifiers verified against ClinicalTrials.gov and PubMed. Machine-readable dataset: studies.json · studies.csv.
What remains unknown
Across this topic, the recurring gap is the same: the randomized evidence describes approved products at studied doses, while compounded and deliberately sub-therapeutic 'microdose' use sits outside it. This page marks that boundary rather than blurring it.
What the evidence shows
- The cited trials carry verified NCT, PMID, and DOI identifiers and studied approved products at labeled doses.
- Findings here reflect those trials' actual results and populations.
What the evidence does not show
- That a compounded or microdose version reproduces these results — it has not been studied.
- That approved-product evidence transfers automatically to compounded formulations.
Frequently asked questions
What did SURMOUNT-4 show?
Continuing tirzepatide maintained weight loss; stopping led to significant regain.
Is regain a class effect?
STEP 4 and SURMOUNT-4 together suggest yes — it's seen with both molecules.
Related: evidence database · research hub. Compounded medications are not FDA approved.
Not medical advice. This page is consumer education, not medical advice, and does not recommend a dose, product, or provider. Compounded medications are not FDA approved. Talk with a licensed clinician about your situation.