SOURCE-LINKED STUDY SUMMARY
Stopping Tirzepatide: Weight Regain in SURMOUNT-4
PED EVIDENCE INTERPRETATION
Does continuing tirzepatide help maintain weight loss?
After 36 weeks of tirzepatide, switching to placebo led to 14.0% weight regain over the next 52 weeks, while continuing treatment produced another 5.5% loss. These percentages use weight at randomization, not original baseline. [1]
- Design
- Randomized withdrawal after a 36-week open-label lead-in
- Population
- 670 randomized adults with overweight or obesity, without diabetes
- Comparison
- Continue tirzepatide 10/15 mg weekly vs switch to placebo
- Duration
- 52 randomized weeks; 88 weeks total
The evidence at a glance
| Outcome | Continue tirzepatide | Switch to placebo | Uncertainty / meaning |
|---|---|---|---|
| Body-weight change [1] | −5.5% | +14.0% | Difference −19.4 percentage points; 95% CI −21.2 to −17.7 |
| Kept ≥80% of initial loss [1] | 89.5% | 16.6% | Key secondary outcome; P < .001 |
| Waist change [1] | −4.3 cm | +7.8 cm | Difference −12.1 cm; 95% CI −13.5 to −10.6 |
OUR READING OF THE EVIDENCE
What this changes
The randomized comparison supports continued treatment for weight maintenance in this selected population. Lifestyle intervention continued in both groups. [1]
What it does not establish
It does not establish the minimum effective maintenance dose, outcomes in diabetes, or lifetime safety. People unable to reach the maintenance phase are not represented by the randomized comparison. [1]
Put it in context
A similar withdrawal pattern with semaglutide
STEP 4 also found an advantage for continuing treatment after a run-in. It supports the broader maintenance question, but comparing effect sizes across separate trials cannot establish which drug is better. [2]
Read the related study summaryThe decision this trial leaves open
Continuation versus withdrawal is a narrower choice than full-dose versus lower-dose maintenance. A result from the first comparison cannot identify the best answer to the second. [1]
Sources and transparency
Eli Lilly sponsored and participated in the study. Gastrointestinal adverse events were more frequent with continued tirzepatide; lead-in selection matters when interpreting tolerability. [1]
Questions this study helps answer
Does SURMOUNT-4 establish the lowest maintenance dose?
No. Participants continued their maximum tolerated 10 or 15 mg weekly dose or switched to placebo. Lower-dose maintenance and tapering were not compared. [1]
Did lifestyle support also stop?
No. Lifestyle intervention continued in both randomized groups. The comparison therefore helps isolate the effect of continuing medication among participants who reached randomization. [1]
Original compact summary and study details
- What was studied
- Randomized withdrawal trial comparing continued tirzepatide with switching to placebo after initial tirzepatide treatment.
- Who / model studied
- 670 adults with obesity or overweight without diabetes completed 36 weeks of initial treatment, then entered a further 52-week randomized comparison.
- Studied dose & schedule
- Dose and schedule have not yet been extracted for this summary.
- What the study found
- After initial average weight loss of 20.9%, weight fell another 5.5% with continued tirzepatide but rose 14.0% after switching to placebo. For the key secondary outcome, 89.5% versus 16.6% maintained at least 80% of their initial weight loss. Digestive adverse events were more common with continued tirzepatide.
- Limitations & context
- The randomized comparison included people who had completed the initial tirzepatide treatment period.
Read summary source ↗ · Prepared 9/16/2026 · AI-assisted, source-based summary
Review record & corrections
Summary prepared: . Source scope: abstract. This is an AI-assisted source summary, not an independent clinician sign-off.
No public field-by-field revision history is available for this card yet. The date above is the summary date, not proof that every field was updated then.
Inspect the source · Correction policyResearch findings apply to the population and conditions studied. This educational summary is not a treatment recommendation or a formal assessment of study quality.
Original publication ↗ · DOI: 10.1001/jama.2023.24945