Tirzepatide for Weight Management after Withdrawal — the SURMOUNT-4 Randomized Clinical Trial — VialBase Research

Summary

SURMOUNT-4 used a randomized withdrawal design to evaluate weight maintenance with continued tirzepatide versus placebo after a 36-week open-label lead-in. After achieving ~21% weight loss during the lead-in, participants who continued tirzepatide maintained and extended their weight loss, while those switching to placebo experienced significant regain.

Key Findings

• After 36-week lead-in: mean weight loss of ~20.9% across all participants
• Continued tirzepatide: additional weight loss to -25.3% at 88 weeks
• Switched to placebo: regained to -9.9% at 88 weeks (partial regain of ~half the lost weight)
• Treatment difference of 17.9 percentage points at 52 weeks post-randomization
• Cardiometabolic improvements largely maintained with continued treatment and partially reversed with placebo
• Similar pattern to STEP 4 (semaglutide withdrawal trial)

Methodology

Randomized withdrawal design. 670 adults with obesity completed 36-week open-label tirzepatide (maximum tolerated dose 10 or 15mg), then randomized 1:1 to continue tirzepatide or switch to placebo for 52 weeks. Primary endpoint: percent weight change from randomization to week 88.

Limitations

• Withdrawal design selects for responders/tolerators during open-label phase
• Does not test dose reduction or tapering strategies
• Half of weight lost was regained within 52 weeks of stopping — concerning trajectory
• Doesn’t evaluate intermittent or maintenance-dose strategies
• Relatively short follow-up after discontinuation (52 weeks)

Relevance to Content

Mirrors STEP 4 findings for semaglutide — chronic treatment is needed. Critical for honest content about treatment expectations. The 25.3% total weight loss with continued treatment is the highest achieved in any major obesity trial. Useful for “what to expect” and treatment planning content.

See Also

• Parent compound: Tirzepatide
• Semaglutide