Trial summary

SURMOUNT-4: what happens on withdrawal

The trial that asked what a course of tirzepatide is worth after it stops. For anyone comparing monthly prices, it is the most consequential trial in this corpus.

Participants

670 randomized

Duration

88 weeks

Comparator

Placebo, by withdrawal of tirzepatide

Published

JAMA, 2024

Registration

NCT04660643

PubMed

PMID 38078870

Who was in the trial

Adults with a BMI of 30 or more, or 27 or more with a weight-related complication, diabetes excluded, who had already completed a 36-week open-label course of tirzepatide. Of 783 who entered the lead-in, 670 were randomized. Mean age was 48 years and mean weight at entry 107.3 kg.

This is a selected group by construction: everybody randomized had already tolerated 36 weeks of tirzepatide and responded to it. That makes the trial a clean measurement of withdrawal and a poor measurement of what happens to a population starting from zero.

How it was run

Phase 3 randomized-withdrawal trial at 70 sites in four countries. A 36-week open-label lead-in on the maximum tolerated dose of tirzepatide (10 mg or 15 mg) was followed by 52 weeks in which participants were reassigned 1:1 to continue tirzepatide or to switch to placebo, double-blind.

Mean percent change in weight from week 36, the point of randomization, to week 88.

A randomized-withdrawal design is unusual and it is the reason the result is interpretable. Both arms had lost weight the same way, on the same medication, over the same 36 weeks. The only thing that then differed was whether the injections continued.

What it found

Over the 52 weeks after randomization, weight changed by -5.5% in the 670 participants who continued tirzepatide and by +14.0% in those switched to placebo — a difference of 19.4 percentage points, in a group that had lost a mean 20.9% during the open-label lead-in.

The maintenance endpoint tells the same story in plainer terms: 89.5% of those continuing held at least 80% of the weight they had lost, against 16.6% of those withdrawn. Across the whole 88 weeks, mean reduction from the starting point was 25.3% with continued tirzepatide and 9.9% with placebo.

The trial’s own conclusion is that withdrawing tirzepatide led to substantial regain of lost weight, while continued treatment maintained and added to the initial reduction.

Why this changes what a monthly price means

A single month’s price is the least useful number a reader can take from a seller’s page, because SURMOUNT-4 measured what happens on stopping and it is not a plateau. The comparison that matters is between sustained costs over a year or longer, not between first-month promotional rates.

That is why our index restates every advertised figure as a true calendar month before comparing sellers: a rate billed every four weeks arrives thirteen times a year, and over a course this length the difference is not rounding. Whether to continue, stop or never start a medication is a decision for a reader and their clinician, and nothing here is advice on it.