SURMOUNT-MAINTAIN design paper published

Researchers led by Deborah B. Horn have published the rationale, design, and baseline data for SURMOUNT-MAINTAIN, a Phase 3b trial testing whether tirzepatide (sold as Zepbound and Mounjaro) can be reduced to 5 mg per week and still keep off weight lost at higher doses ^[1]. The paper, funded by Eli Lilly and appearing in the journal Obesity on September 7, 2025, describes a study that enrolled 441 participants with obesity, most of them female, with a mean BMI of 40 kg/m2 ^[1].

The trial starts with a 60-week period in which all participants take tirzepatide at their maximum tolerated dose, either 10 mg or 15 mg weekly, without knowing what comes next ^[1]. Those who reach a "body weight plateau," defined as less than 5% weight change between weeks 48 and 60, are then randomly assigned to one of three paths for an additional 52 weeks: staying on the maximum dose, dropping to 5 mg, or switching to a placebo ^[1]. The main question the trial will answer is how much of the weight lost during the first phase is still gone at week 112 ^[1].

Baseline data show a study population with an average age of 47, average body weight of 114 kg, and average waist circumference of 119 cm ^[1]. People with type 2 diabetes were excluded, and participants qualified with a BMI of 30 or higher, or 27 or higher with at least one weight-related health condition ^[1].

The design responds to a problem seen in earlier trials. In SURMOUNT-4, participants lost an average of 21% of body weight during a 36-week tirzepatide lead-in, but those switched to placebo regained 14% of that weight ^[1]. A similar pattern showed up in the STEP 4 trial of semaglutide, where participants regained 7% of body weight after being switched to placebo following a 20-week run-in ^[1]. In an extension of the STEP 1 trial, participants who stopped semaglutide and stayed on a lifestyle program still regained about two-thirds of the weight they had lost within a year ^[1]. The paper describes obesity as a chronic disease where stopping treatment tends to bring rapid weight regain, even with continued diet and exercise support ^[1].

The trial also introduces a rescue plan: participants who regain half or more of the weight they lost during the weight-loss phase can receive tirzepatide again, called "medication rescue" in the paper ^[1].

Why it matters for patients

Many people currently on tirzepatide or considering it worry about what happens if they can no longer afford or tolerate the highest dose. This trial is designed to test, for the first time in a randomized way, whether a lower 5 mg maintenance dose is enough to hold onto weight loss, compared with staying on the full dose or stopping altogether ^[1]. Prior data already suggest that stopping GLP-1 or dual GIP/GLP-1 treatment tends to lead to weight regain, sometimes substantial, within months ^[1]. This trial won't change anything about current prescriptions on its own, since it is still in progress, but its results could eventually help patients and clinicians decide whether tapering to a lower dose is a reasonable option for long-term maintenance, as opposed to staying at the highest tolerated dose indefinitely.

What happens next

The paper reports an anticipated trial completion date of May 2026 ^[1]. The study, registered as NCT06047548, is described as still in progress, with the primary result — percent maintenance of weight loss at week 112 — not yet available ^[1]. Until final results are published, it is not known whether the lower 5 mg dose will match the maintenance seen with the full dose, or how it will compare with placebo.