SURMOUNT-MAINTAIN compares maximum-tolerated, 5 mg, and withdrawn tirzepatide after initial loss

What happened

SURMOUNT-MAINTAIN tested three strategies after an initial 60 weeks of tirzepatide treatment in adults with obesity. Participants either continued their maximum tolerated weekly dose, moved down to 5 mg, or received placebo during a 52-week randomized maintenance phase.

The U.S. phase 3b trial began with 441 participants receiving open-label tirzepatide. At week 60, 378 were randomized: 140 to continue a maximum tolerated dose of 10 mg or 15 mg, 144 to use 5 mg, and 94 to switch to placebo. Of those randomized, 372 received at least one maintenance-phase dose and 345, or 91%, completed the full 112 weeks.

The randomized population had an average age of 46.6 years; 65% were women and 67% were White. Average weight before the initial treatment phase was 113.8 kilograms, and average BMI was 40.1. These characteristics describe the trial group and are relevant when considering how well its averages may transfer to other populations.

At week 112, the model placed the maximum-tolerated-dose group 21.9% below its original starting weight. The 5 mg group remained 16.6% below baseline; the placebo group remained 9.9% below it. Relative to placebo, continued maximum dosing improved the estimate by 12.0 percentage points, while 5 mg improved it by 6.6 points. Each comparison met the trial's statistical threshold.

Starting 24 weeks after randomization, the protocol allowed rescue tirzepatide for participants who regained more than half of the weight they had lost before randomization. Rescue was used by 11 of 138 evaluable participants, or 8%, on the maximum tolerated dose; 35 of 142, or 25%, on 5 mg; and 60 of 90, or 67%, after switching to placebo.

Digestive-system events were the most common adverse effects during tirzepatide treatment. They were usually mild or moderate and occurred mainly while doses were being increased. Eli Lilly funded the study, and several authors were company employees or reported industry relationships.

What it means

The randomized phase answers a practical question about maintaining a prior response. Staying at 10 mg or 15 mg produced the largest average reduction at week 112. Reducing to 5 mg preserved less, but still more than stopping active treatment under the study protocol.

The trial also shows why a single final percentage does not capture every participant's course. Rescue use was much more frequent after withdrawal, and individual response varied within each group.

What it does not mean

The study does not establish one maintenance dose for everyone. Participants first tolerated and completed a long open-label phase, and those who reached randomization may differ from people who discontinue earlier. The study also did not test every possible taper, dosing interval, alternative medicine, nutrition program, or combination strategy.

The placebo group's 9.9% average reduction should not be interpreted as equal maintenance after withdrawal. It is measured from the original baseline after participants had already lost substantial weight during the first 60 weeks, and many placebo participants later met the rescue criterion.

Follow-up ended at 112 weeks, so the trial cannot establish the best lifelong strategy or uncommon long-term harms. The result supports a clinician-patient maintenance discussion, not unsupervised dose reduction.