Trial summary

SURMOUNT-1: tirzepatide for obesity

The trial that established what tirzepatide does to body weight in people who do not have diabetes, and the one every later weight figure is measured against.

Participants

2,539 randomized

Duration

72 weeks

Comparator

Placebo

Published

New England Journal of Medicine, 2022

Registration

NCT04184622

PubMed

PMID 35658024

Who was in the trial

Adults with a BMI of 30 or more, or 27 or more with at least one weight-related complication. People with diabetes were excluded. Mean baseline weight was 104.8 kg and mean BMI was 38.0.

The exclusion matters more than it looks. Because diabetes was an exclusion, SURMOUNT-1 does not tell a reader what tirzepatide does to the weight of somebody with type 2 diabetes, where weight loss is consistently smaller. For that population the relevant trial is SURPASS-2.

How it was run

Phase 3, double-blind, randomized and placebo-controlled, running 72 weeks and including a 20-week dose-escalation period. Participants were assigned 1:1:1:1 to tirzepatide 5 mg, 10 mg or 15 mg, or to placebo, once weekly by subcutaneous injection.

Two co-primary endpoints: the percentage change in body weight from baseline at week 72, and the proportion of participants losing 5% of body weight or more.

The 20-week escalation is part of why the trial ran 72 weeks. Nobody started at the dose their result is attributed to; they climbed to it over roughly five months, which is the same reason a dose ladder appears on seller pricing pages.

What it found

Those are mean percentage changes in body weight from baseline at week 72, in 2,539 adults, against placebo. The 5 mg group changed by -15.0%. The trial reported confidence intervals of roughly one percentage point either side of each figure, and P<0.001 for every comparison with placebo.

The second co-primary endpoint was the share of participants losing 5% or more: 85%, 89% and 91% at 5, 10 and 15 mg against 35% on placebo. At the harder threshold of 20% or more, 57% of the 15 mg group and 50% of the 10 mg group reached it, against 3% on placebo.

A mean is not a personal forecast, and the trial’s own thresholds show the spread: 57% of the 15 mg group reached a 20% reduction, which is also to say that 43% of them did not. The trial published no result at all for a compounded preparation.

What was reported about tolerability

The most common adverse events on tirzepatide were gastrointestinal, mostly mild to moderate, and they occurred primarily during dose escalation rather than at the top dose. Adverse events caused discontinuation in 4.3%, 7.1% and 6.2% of the 5, 10 and 15 mg groups and 2.6% of the placebo group.

Side effects are a matter for a prescriber who knows the person in front of them. This page reports what the trial recorded; it is not a safety assessment and it is not medical advice.

Reading this alongside the price index

SURMOUNT-1 tested the approved product at a fixed, supervised dose ladder for 72 weeks. A compounded vial priced on our index is a different preparation, and the 72-week course the trial ran is the horizon a monthly price should be multiplied over before it is compared with anything.