SURMOUNT-1: tirzepatide 5, 10 and 15 mg for obesity over 72 weeks

SURMOUNT-1 is the trial behind the Zepbound approval and the trial most people mean when they quote "over 20 percent" for tirzepatide. This digest reports what its primary publication says, and only that.

What the trial asked

Whether once-weekly tirzepatide, a combined GIP and GLP-1 receptor agonist, reduces body weight in adults with obesity or overweight who do not have diabetes, and how much of that reduction depends on dose.

Design

Phase 3, double-blind, randomised, placebo-controlled. Participants were assigned 1:1:1:1 to tirzepatide 5 mg, 10 mg, 15 mg or placebo, injected once a week for 72 weeks. The first 20 weeks were a dose-escalation period. All arms had the same lifestyle programme.

The primary analysis used the treatment-regimen estimand: effects were assessed regardless of whether a participant stopped treatment, in the intention-to-treat population. That matters when you compare this number with other trials; see how to read a GLP-1 trial.

Who was enrolled

2539 adults with a BMI of 30 or more, or 27 or more with at least one weight-related complication. People with diabetes were excluded. At baseline the mean body weight was 104.8 kg and the mean BMI 38.0; 94.5 percent had a BMI of 30 or higher.

Primary endpoint and result

Two coprimary endpoints at week 72: the percent change in weight from baseline, and the share of participants losing 5 percent or more.

P was below 0.001 for every tirzepatide arm against placebo.

The share reaching a 5 percent reduction was 85 percent (95% CI 82 to 89) on 5 mg, 89 percent (86 to 92) on 10 mg and 91 percent (88 to 94) on 15 mg, against 35 percent (30 to 39) on placebo.

Key secondary results

A 20 percent or greater reduction was reached by 50 percent (95% CI 46 to 54) of the 10 mg group and 57 percent (53 to 61) of the 15 mg group, versus 3 percent (1 to 5) on placebo. The abstract states that all prespecified cardiometabolic measures improved with tirzepatide but does not give the figures.

Adverse events and discontinuation

The most common adverse events were gastrointestinal, mostly mild to moderate, and concentrated in the dose-escalation period. Adverse events led to treatment discontinuation in 4.3 percent (5 mg), 7.1 percent (10 mg), 6.2 percent (15 mg) and 2.6 percent (placebo).

Funding and registration

Supported by Eli Lilly. ClinicalTrials.gov NCT04184622.

What this trial does not show

• It does not show what happens after week 72, or after stopping. That question went to SURMOUNT-4.
• It does not compare tirzepatide with semaglutide. That comparison is SURMOUNT-5.
• It excluded people with diabetes, whose results in SURMOUNT-2 were smaller.
• It says nothing about hard outcomes such as heart attack or stroke.
• It did not study compounded tirzepatide, which is not FDA approved and was not the product tested.

Where the numbers come from

All figures above are from the PubMed abstract of the primary paper (PubMed 35658024), fetched from the NCBI database on 4 September 2026. The abstract does not report the confidence intervals for the individual responder thresholds beyond those quoted, nor the specific cardiometabolic values, so they are not repeated here. For the broader picture of tirzepatide, the FormBlends tirzepatide complete guide covers dosing and practical questions, and the calculator site applies these arm averages to a body weight.