Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial.

Weight reduction and its maintenance play an important role in achieving these goals.

减重及其维持在实现这些目标中扮演着重要角色。

We evaluated the efficacy and safety of continuing tirzepatide at the maximum tolerated dose (MTD) or lowering the dose to 5 mg compared with switching to placebo on the maintenance of bodyweight reduction obtained with tirzepatide MTD in adults with obesity.

我们评估了在成人肥胖患者中，维持使用最大耐受剂量（MTD）的tirzepatide或降低剂量至5 mg，与切换至安慰剂相比，在维持tirzepatide MTD获得的体重减轻方面的疗效和安全性。

Methods

This phase 3b, placebo-controlled, 112-week trial, including a 60-week open-label weight-loss period and a 52-week, double-blindweight maintenance period, was conducted across 20 sites in the USA.

这项为期112周的3b期、安慰剂对照试验，包括一个为期60周的开放标签减重期和一个为期52周的双盲体重维持期，在美国的20个地点进行。

After completing the initial weight-loss period with once weekly subcutaneous tirzepatide at the MTD (10 mg or 15 mg), adults (aged ≥18 years) with a BMI of 30 kg/m2 and above or 27 kg/m2 and above with one or more weight-related comorbidity, and a history of at least one self-reported unsuccessful dietary effort to lose bodyweight were randomly assigned in a 3:3:2 ratio to continue tirzepatide MTD, reduce to tirzepatide 5 mg, or switch to placebo for an additional 52 weeks.

在完成初始减重期后，体重指数（BMI）≥30 kg/m2或≥27 kg/m2伴有至少一种与体重相关的共病，并且至少有一次自我报告的减重饮食尝试失败的成年人（年龄≥18岁），按3:3:2的比例随机分配继续使用最大耐受剂量（MTD）的每周一次皮下注射tirzepatide，减少至5 mg的tirzepatide，或转为安慰剂，额外治疗52周。

Starting at week 84 (24 weeks after random allocation), participants could receive rescue tirzepatide if their weight regain exceeded 50%.

从第84周（随机分配后24周）开始，如果参与者的体重反弹超过50%，则可以接受tirzepatide救援治疗。

The primary endpoint was the percentage change in bodyweight from baseline to week 112.

主要终点是从基线到第112周体重变化的百分比。

The primary estimand was the modified treatment-regimen estimand, which assumed that participants who initiated rescue tirzepatide would not have gained further benefit from their assigned study treatment and included all randomly allocated participants, regardless of treatment discontinuation or initiation of prohibited medications.

主要估计量是修改后的治疗方案估计量，假设开始使用救援药物tirzepatide的参与者不会从他们分配的研究治疗中获得进一步的益处，并包括所有随机分配的参与者，无论治疗中断或开始使用禁止的药物。

The efficacy estimand was supportive.

疗效估计量是支持性的。

Safety was assessed in all participants who received at least one dose of study drug.

安全性评估在所有至少接受一次研究药物剂量的参与者中进行。

This completed trial was registered at ClinicalTrials.gov (NCT06047548).

这项已完成的试验已在ClinicalTrials.gov注册（NCT06047548）。

Results

From Sept 20, 2023, to Jan 20, 2026, 441 patients were enrolled in and took at least one dose of study treatment during the weight-loss period, with 378 participants randomly allocated at week 60 (140 to tirzepatide MTD; 144 to dose-reduction to 5 mg tirzepatide; and 94 to placebo). 372 received at least one dose of study drug during the weight maintenance period (139 for tirzepatide MTD; 142 for 5 mg tirzepatide; and 91 for placebo). 345 (91%) of 378 participants completed the study.

从2023年9月20日至2026年1月20日，共有441名患者在减重期间至少接受了一次研究治疗，其中378名参与者在第60周被随机分配（140名接受tirzepatide最大耐受剂量（MTD）；144名减少剂量至5 mg tirzepatide；94名接受安慰剂）。

The majority of participants were White (67%); 288 (65%) participants were female and 153 (35%) were male; and the mean age was 46·6 years (SD 13·0).

大多数参与者是白人（67%）；288名（65%）参与者为女性，153名（35%）为男性；平均年龄为46.6岁（标准差13.0）。

At baseline, participants had a mean bodyweight of 113·8 kg (SD 27·0), a BMI of 40·1 kg/m2 (SD 8·1), and HbA1c 5·64% (SD 0·4; 38·2 mmol/mol [SD 4·0]).

在基线时，参与者的平均体重为113.8公斤（标准差27.0），BMI为40.1公斤/平方米（标准差8.1），HbA1c为5.64%（标准差0.4；38.2毫摩尔/摩尔[标准差4.0]）。

The model-based estimate percent change in bodyweight from baseline to week 112 was -21·9% (95% CI -23·5 to -20·3) with MTD (estimated treatment difference [ETD] -12·0% [95% CI -13s·8 to -10·1]), -16·6% (95% CI -18·0 to -15·1) with 5 mg tirzepatide (ETD -6·6 [95% CI -8·3 to -5·0]), versus -9·9% (95% CI -11·1 to -8·8) with placebo (p<0·0001 for all comparisons).

从基线到第112周，基于模型的体重变化百分比估计为-21.9%（95%置信区间-23.5至-20.3），MTD组（估计治疗差异[ETD]为-12.0% [95%置信区间-13.8至-10.1]），5毫克tirzepatide组为-16.6%（95%置信区间-18.0至-15.1）（ETD为-6.6 [95%置信区间-8.3至-5.0]），与安慰剂组的-9.9%（95%置信区间-11.1至-8.8）相比（所有比较的p<0.0001）。

Among participants who regained at least 50% of lost bodyweight, observed means were 11 (8%) of 138, 35 (25%) of 142, and 60 (67%) of 90 participants received rescue therapy in the tirzepatide MTD, 5 mg tirzepatide, and placebo, respectively.

在体重至少恢复了50%的参与者中，观察到的平均值分别为11（8%）的138名、35（25%）的142名和60（67%）的90名参与者分别在tirzepatide MTD、5毫克tirzepatide和安慰剂组接受了救援治疗。

The most common adverse events with tirzepatide were gastrointestinal events, which were mostly mild to moderate in severity and mostly occurred during dose escalation.

接受tirzepatide治疗的患者中最常见的不良事件是胃肠道事件，这些事件大多为轻度至中度，并且大多在剂量递增期间发生。

interpretation

In adults with obesity, long-term treatment is often necessary to maintain bodyweight reduction and its associated cardiometabolic benefits.

对于肥胖成人来说，为了维持体重减轻及其相关的代谢心血管益处，通常需要长期治疗。

In the SURMOUNT-MAINTAIN trial, continuing tirzepatide at MTD maintained bodyweight reduction and health-related benefits.

在SURMOUNT-MAINTAIN试验中，继续使用最大耐受剂量（MTD）的tirzepatide维持了体重减轻和健康相关益处。

Reducing to 5 mg tirzepatide might provide a valuable alternative to discontinuation, although individuals' treatment response might vary.

将tirzepatide剂量减少至5毫克可能为停药提供了一个有价值的替代方案，尽管个体的治疗反应可能会有所不同。

Together, these findings support the importance of ongoing therapy for long-term obesity management and provide evidence to inform individualised, patient-centred obesity care.

这些发现共同支持了长期肥胖管理中持续治疗的重要性，并提供了证据以指导个体化、以患者为中心的肥胖护理。

funding

Eli Lilly.

礼来制药。