SURMOUNT-4
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.
Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, Ahmad NN, Zhang S, Liao R, Bunck MC, Jouravskaya I, Murphy MA, SURMOUNT-4 Investigators. · JAMA
Study record
- Population
670 adults without diabetes randomized after a 36-week tirzepatide lead-in; 335 per arm.
Read source · Full-text reportAbstract — Design and Results; Table 1- Formulation
Tirzepatide versus matched placebo.
Read source · Full-text reportMethods — Procedures- Route
Subcutaneous.
Read source · Full-text reportMethods — Procedures- Dose & frequency
Lead-in: 2.5 mg weekly, escalating by 2.5 mg every four weeks to tolerated 10/15 mg; then continuation or placebo.
Read source · Full-text reportMethods — Procedures- Study design
Double-blind randomized withdrawal following open-label treatment.
Read source · Full-text reportMethods — Study Design- Duration
36-week lead-in plus 52-week randomized treatment.
Read source · Full-text reportMethods — Study Design- Reported findings
Week-36-to-88 weight change: −5.5% versus +14.0%; treatment-regimen difference −19.4 percentage points (95% CI −21.2 to −17.7).
Read source · Full-text reportAbstract Results; Table 2; Statistical Analysis- Adverse events
Randomized-period serious events: 3.0% each arm; adverse-event discontinuation: 1.8% versus 0.9%. Lead-in discontinuation was 7.0%.
Read source · Full-text reportTable 3; Adverse Events and Tolerability- Monitoring
Adverse-event and laboratory assessment; selected major events externally adjudicated.
Read source · Full-text reportMethods — Outcomes; Statistical Analysis
What it supports
Continuation preserved weight loss better than withdrawal.
What it does not establish
Lead-in selection limits generalization. Does not validate repeated on/off cycles. Registry on-treatment estimates differ because post-discontinuation data are excluded.
Funding
Eli Lilly sponsored and participated in trial design, conduct, analysis and reporting (Article Information).
Publication and registry context
The registry reports weight change of −6.7% with continued tirzepatide versus +14.8% with placebo after randomization, excluding data after treatment discontinuation. The publication figures above use the treatment-regimen analysis. Registry serious events were 10/335 in each randomized arm through week 92; the separate lead-in had 16/782 through week 36. Lead-in participants overlap the randomized groups and must not be added to them.
Inspect NCT04660643 resultsLiterature search cutoff: 2026-09-08 · Not independently clinically reviewed
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