Direct study · 2023

SURMOUNT-3

Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial.

Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. · Nature medicine

Study record

Population: 579 adults without diabetes who first lost at least 5% of body weight during a 12-week intensive lifestyle program; 287 assigned tirzepatide and 292 placebo.
Read source · Full-text reportMethods — Study design and participants; Table 2
Formulation: Tirzepatide or matching placebo supplied in visually identical single-dose pens.
Read source · Full-text reportMethods — Randomization; Procedures during the double-blind treatment period
Route: Subcutaneous injection once weekly.
Read source · Full-text reportMethods — Procedures during the double-blind treatment period
Dose & frequency: Started at 2.5 mg weekly, increasing by 2.5 mg every four weeks toward a tolerated 10 or 15 mg. Protocol-limited de-escalation/re-escalation addressed intolerance during the first 24 weeks; this is not a general cycling schedule.
Read source · Full-text reportMethods — Procedures during the double-blind treatment period
Study design: Phase 3, double-blind, 1:1 randomized trial after lifestyle-response selection. Continued lifestyle counseling accompanied both arms.
Read source · Full-text reportMethods — Randomization; Procedures
Duration: 12-week lifestyle lead-in, then 72-week randomized treatment including escalation, followed by four-week safety follow-up.
Read source · Full-text reportMethods — Study design and participants
Reported findings: Additional weight change from randomization to week 72: −18.4% versus +2.5% with placebo; difference −20.8 percentage points (95% CI −23.2 to −18.5). Treatment-regimen analysis includes discontinuation and hybrid missing-data imputation.
Read source · Full-text reportAbstract; Results; Methods — Statistical analysis
Adverse events: Serious adverse events: 5.9% versus 4.8%; adverse-event discontinuation: 10.5% versus 2.1%. Gastrointestinal events predominated. Events during treatment are not necessarily caused by treatment.
Read source · Full-text reportResults — Safety; Table 3
Monitoring: Adverse events and additional safety measures were assessed through treatment and safety follow-up; Table 3 separates serious, discontinuation and selected events.
Read source · Full-text reportResults — Safety; Table 3; Extended Data Table 3

What it supports

Assesses additional weight loss after successful intensive lifestyle intervention.

What it does not establish

Selected lifestyle responders, not all people starting treatment. Corrected Figure 2 b/f legends must be used: treatment labels were originally swapped. This does not establish a stop-start protocol.

Funding

Eli Lilly funded the trial and participated in design, oversight and writing support (Acknowledgements).

Publication and registry context

The registry reports weight change of −21.1% versus +3.3% over 72 weeks after randomization, excluding data after treatment discontinuation. At least 5% weight loss was reported in 94.37% versus 10.65%. These are different analyses from treatment-regimen estimates and exclude the preceding lifestyle-intervention period from the weight-change baseline. Registry serious events were 17/287 versus 14/292 through week 76.

Inspect NCT04657016 results

Literature search cutoff: 2026-09-08 · Not independently clinically reviewed

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