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ISTANBUL — Continuing tirzepatide helped adults without diabetes maintain far more of their initial weight loss than stopping the drug, with the strongest effect seen in those who stayed on their maximum tolerated dose, according to results from the SURMOUNT-MAINTAIN trial.

Among participants who had reached a bodyweight plateau, at least 80% of the weight lost during the initial treatment phase was maintained at week 112 by 77.5% of those who continued the maximum dose of tirzepatide (10 mg or 15 mg), 42.4% of those who stepped down to 5 mg, and 10.4% of those switched to placebo.

“I think SURMOUNT-MAINTAIN is so interesting because it addresses probably the number one question I get from patients who have responded successfully to treatment,” said Deborah Horn, DO, director of the Center for Obesity Medicine and Metabolic Performance at McGovern Medical School at UTHealth Houston in Houston. “They ask: Do I need to stay on this dose? Could I go on a lower dose and still keep the weight off? Could I stop the medication and maintain the weight loss?”

Horn presented the findings at the 33rd European Congress on Obesity (ECO) 2026. The study was published simultaneously in The Lancet.

Two-Phase Trial

The SURMOUNT-MAINTAIN trial was a US-based, multicenter, double-blind, randomized, placebo-controlled trial conducted at 20 sites. At study start, participants had a mean body weight of 113.8 kg, a BMI of 40.1, and A1c of 5.64%.

The trial comprised a 60-week open-label phase in which 441 participants received once weekly tirzepatide, starting at 2.5 mg and escalating every 4 weeks to a maximum tolerated dose of 10 mg or 15 mg. After this phase, participants who had lost at least 5% of body weight and tolerated at least 10 mg of tirzepatide were eligible for randomization; most, but not all, had achieved bodyweight stability.

At week 60, 378 participants were randomized in a 3:3:2 ratio to continue tirzepatide at the maximum tolerated dose (n = 140), reduce to tirzepatide 5 mg (n = 144), or switch to placebo (n = 94) for a further 52 weeks. The primary endpoint was percent change in body weight from baseline to week 112.

Starting at week 84, participants who regained at least 50% of the weight they had lost during the initial treatment phase could receive rescue tirzepatide.

“We already knew from SURMOUNT-4 what happens when you stop treatment,” Horn said. “What we really wanted to know here was whether someone could maintain benefit on a lower dose.”

She also noted that rescue therapy was used by 8% of participants continuing the maximum tolerated dose of tirzepatide, 24.6% of those reduced to 5 mg, and 66.7% of those switched to placebo.

“That tells you what was happening in the placebo group,” she said. “People were regaining significant weight.”

Full Dose Best, but Lower Dose Helped Maintenance

After the initial 60-week weight-loss phase, continued tirzepatide treatment was superior to placebo for maintaining weight loss, whether participants remained on their maximum tolerated dose or stepped down to 5 mg.

Before rescue therapy was allowed in the double-blind phase, weight regain was already evident among participants switched to placebo. At 24 weeks after randomization, those who continued the maximum tolerated dose of tirzepatide had lost 22.4% of their baseline body weight, compared with 18.8% among those reduced to tirzepatide 5 mg and 12.3% among those switched to placebo.

“So you can see the regain trajectory happening [in those randomized to placebo],” Horn said.

She added that if rescue therapy had not been permitted, participants in the placebo group were estimated to have regained enough weight that, by week 112, they would have retained only a 4.8% reduction from their baseline body weight. 

Under the efficacy estimand, placebo recipients had lost an average of 10.1% of their baseline body weight by week 112. By comparison, participants who continued the maximum tolerated dose of tirzepatide had maintained a 22.4% reduction from baseline body weight, whereas those reduced to 5 mg had maintained a 17% reduction.

“You can see there’s a clear difference between staying on maximum tolerated dose, reducing to 5 mg, or moving to placebo,” Horn said.

She also emphasized the high study completion rate, with more than 91% of randomized participants completing the trial.

“In this day and age, when patients have access to many obesity treatments outside trials, that’s a real accomplishment.”

Among participants who had reached a bodyweight plateau before randomization, those who continued the maximum tolerated dose of tirzepatide maintained nearly all the weight reduction achieved during the initial weight-loss phase. Under the efficacy estimand, they maintained 100% of that reduction at week 112 compared with 70.5% among those reduced to 5 mg and 44.3% among those switched to placebo.

Using the primary treatment-regimen estimand, at least 80% of the initial weight loss was maintained by 77.5% of participants continuing the maximum tolerated dose of tirzepatide, 42.4% of those reduced to 5 mg, and 10.4% of those switched to placebo.

Cardiometabolic Benefits Followed Weight

Cardiometabolic improvements broadly mirrored the weight findings. Systolic blood pressure fell during the open-label tirzepatide phase and remained lowest among those who continued maximum-dose treatment. It rose modestly among those switched to 5 mg and increased further among placebo recipients.

Lipid findings followed a similar pattern. For triglycerides, participants continuing the maximum tolerated dose of tirzepatide maintained roughly a 27% improvement, compared with 19% with tirzepatide 5 mg and 9.6% with placebo from baseline.

“We really see a difference between whether the patient stays on medication, even low-dose medication vs placebo,” Horn remarked.

No New Safety Signals

The safety profile was consistent with previous tirzepatide trials. The most common adverse events were gastrointestinal, including nausea, vomiting, and diarrhea, and were mostly mild to moderate. During the maintenance period, nausea, vomiting, or diarrhea occurred in 14% of participants continuing the maximum tolerated dose of tirzepatide, 7% of those reduced to 5 mg, and 3% of those switched to placebo.

“The GI [gastrointestinal] adverse events float to the top, just as they have in every other tirzepatide trial,” Horn said. “Nothing surprising. That reassures me as a clinician that tirzepatide is tirzepatide is tirzepatide.”

Most GI events occurred during the initial dose-escalation phase.

Individualized Dosing Supported

Horn said the findings support shared decision-making, particularly when patients want or need to reduce their dose. “If someone either desires or there’s an indication for changing medications or going to a lower dose, SURMOUNT-MAINTAIN helps reassure us that many clinically meaningful outcomes persist even at a lower dose,” she said, adding that the trial helps move obesity treatment toward more individualized care.

“You can really think about the person sitting in front of you and decide together, through shared decision-making, what is best for them,” Horn said. “We knew this intuitively as clinicians, but now we have the science and data to advise patients on what that looks like and what they can expect.”

Asked about lifestyle, Horn said, all participants received nutritional and physical activity support, although activity was self-reported.

“As people feel better and lose weight, they’re more likely to move more, be more active, and possibly make better nutritional choices,” she said.

Fills an Important Evidence Gap

André J. Scheen, MD, from the Liège University in Liège, Belgium, who wrote an accompanying commentary in The Lancet, wrote that the study addressed an important evidence gap by providing “a well designed placebo-controlled RCT [randomized controlled trial] trial, a missing piece of evidence until now,” evaluating dose-reduction strategies after substantial weight loss with tirzepatide.

He noted that the SURMOUNT-MAINTAIN trial was the first obesity trial to investigate “the effect of reducing the dose of an effective obesity medication” on long-term weight maintenance, while also incorporating rescue obesity medication when participants regained at least 50% of lost weight.

Scheen added that the findings suggested that dose reduction “may be considered as a novel patient-centered approach” to help strengthen long-term weight-loss maintenance. However, he cautioned that responses to treatment varied between individuals and that “the study protocol does not allow for detection of which patients will benefit most from the reduced 5 mg tirzepatide strategy,” which he described as “crucial information to guide the clinician” toward more personalized and cost-effective obesity care.

“In this complex topic of major clinical interest, SURMOUNT-MAINTAIN now provides information on the effect of dose reduction on the maintenance of bodyweight reduction for the first time in a dedicated RCT,” Scheen wrote, adding that “more specific research is still warranted” to determine which patients are most likely to successfully maintain weight loss on lower-dose treatment.

Horn reported acting as a consultant and speaker for Eli Lilly and Company and Novo Nordisk; serving as a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Kailera, Roche, and Zealand; and receiving institutional research funding from Eli Lilly and Company, KVK Tech, Novo Nordisk, and Weight Watchers. Scheen reported receiving speaker fees from Eli Lilly, Novo Nordisk, and Boehringer Ingelheim; and travel support from Eli Lilly.