SURMOUNT-4: Tirzepatide Maintenance — Continued versus Withdrawn

Background + significance

SURMOUNT-4 is the trial that establishes GLP-1 as chronic therapy. Patients randomized to withdraw from tirzepatide regained roughly 2/3 of their lost weight within 52 weeks. The clinical implication: GLP-1 for weight management is FDA-labeled for chronic use, and stopping reliably reverses the gains.

Trial design

Sponsor

Eli Lilly

Phase

Phase 3

Participants

783

Duration

88 weeks

ClinicalTrials.gov ID

NCT04657003

Drugs tested

• Zepbound (tirzepatide 15 mg)Active

Primary outcome

Percentage change in body weight from week 36 (randomization) to week 88, in patients randomized to continue tirzepatide vs withdraw to placebo

Continued tirzepatide: additional −5.5% weight loss. Withdrawn to placebo: regained 14% of body weight by week 88 (about 2/3 of weight previously lost).

Secondary outcomes

• •Sustained improvements in BP, lipids, A1C in continuation group
• •Rapid reversal of metabolic improvements in withdrawal group
• •Quality-of-life metrics tracked weight trajectory

Why it matters

1. 1.Patients regain ~2/3 of lost weight within 12 months of stopping.
2. 2.Confirms GLP-1 weight-management is chronic therapy, not a 6-month course.
3. 3.Maps to FDA labeling: stopping a clinician decision, not a graduation milestone.