18+ · Research Use Only · Not for Human Consumption

Tirzepatide · Phase 3 · Completed

SURMOUNT-4

In SURMOUNT-4, a phase 3 trial of tirzepatide in adults with BMI of 30 or more, or 27 or more with a weight-related complication, excluding diabetes (n=670), mean body weight changed by -5.5% on continued tirzepatide, weeks 36 to 88 over 88 weeks, against +14.0% on switched to placebo (treatment-regimen estimand; Aronne LJ et al. JAMA 2024 (SURMOUNT-4)).

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Results

SURMOUNT-4: mean percent change in body weight by armSURMOUNT-4 treatment-regimen estimandContinued tirzepatide, weeks 36 to 88-5.5%Switched to placebo+14.0%
Mean percent change in body weight by arm, as each source reports it. Bars from different trials are not a head-to-head comparison: populations, durations and estimands differ.

Side effects reported

In SURMOUNT-4, discontinuation because of adverse events was 1.8% on continued tirzepatide, weeks 36 to 88, against 0.9% on switched to placebo. The most frequently reported adverse events were diarrhoea in 10.7% on continued tirzepatide, weeks 36 to 88 against 4.8% on switched to placebo, nausea in 8.1% on continued tirzepatide, weeks 36 to 88 against 2.7% on switched to placebo and vomiting in 5.7% on continued tirzepatide, weeks 36 to 88 against 1.2% on switched to placebo.

EventContinued tirzepatide, weeks 36 to 88Switched to placebo
Discontinuation for adverse events1.8%0.9%
Diarrhoea10.7%4.8%
Nausea8.1%2.7%
Vomiting5.7%1.2%

Design

Trial design and sources

Compound
Tirzepatide
Phase
3
Population
Adults with BMI of 30 or more, or 27 or more with a weight-related complication, excluding diabetes
Participants randomised
670
Duration
88 weeks
Primary endpoint
Mean percent change in weight from week 36 (randomization) to week 88
Estimand
treatment-regimen
Read out
1 January 2024

Withdrawal design: a 36-week open-label lead-in on tirzepatide, then randomisation to continue or switch to placebo. The switch-to-placebo arm regained weight. Adverse events shown are the double-blind period.

  • Aronne LJ et al. JAMA 2024 (SURMOUNT-4) open · checked 23 September 2026
  • ClinicalTrials.gov NCT04660643 open · checked 23 September 2026
  • Registry: NCT04660643

Questions

SURMOUNT-4, answered

What did SURMOUNT-4 find?

In SURMOUNT-4, a phase 3 trial of tirzepatide in adults with BMI of 30 or more, or 27 or more with a weight-related complication, excluding diabetes (n=670), mean body weight changed by -5.5% on continued tirzepatide, weeks 36 to 88 over 88 weeks, against +14.0% on switched to placebo (treatment-regimen estimand; Aronne LJ et al. JAMA 2024 (SURMOUNT-4)).

What side effects were reported in SURMOUNT-4?

In SURMOUNT-4, discontinuation because of adverse events was 1.8% on continued tirzepatide, weeks 36 to 88, against 0.9% on switched to placebo. The most frequently reported adverse events were diarrhoea in 10.7% on continued tirzepatide, weeks 36 to 88 against 4.8% on switched to placebo, nausea in 8.1% on continued tirzepatide, weeks 36 to 88 against 2.7% on switched to placebo and vomiting in 5.7% on continued tirzepatide, weeks 36 to 88 against 1.2% on switched to placebo.