美国耶鲁大学医学院Ania M. Jastreboff团队研究了每周一次Tirzepatide治疗肥胖症的疗效。2022年6月4日出版的《新英格兰医学杂志》发表了这项成果。

肥胖症是一种慢性病，在全球范围内导致较高发病率和死亡率。一种新型的葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1受体激动剂Tirzepatide对肥胖患者的疗效和安全性尚不清楚。

在这项临床3期、双盲、随机、对照试验中，研究组招募了2539名体重指数（BMI）为30及以上，或27及以上且至少有一种体重相关并发症（糖尿病除外）的成年人，将其按1：1：1：1的比例随机分组，分别每周接受一次皮下注射tirzepatide（5 mg、10 mg或15 mg）或安慰剂，为期72周，包括20周的剂量递增期。主要终点是体重相对于基线的百分比变化和体重减轻5%及以上。在意向治疗人群中，无论是否中断治疗，治疗方案都会评估疗效。

基线检查时，参与者的平均体重为104.8 kg，平均BMI为38.0，94.5%的参与者BMI为30或更高。5 mg tirzepatide组72周时的体重平均减轻15%，10 mg tirzepatide组平均减轻19.5%，15 mg tirzepatide组平均减轻20.9%，安慰剂组平均减轻3.1%，Tirzepatide三个组与安慰剂组相比差异均显著。

5 mg、10 mg和15 mg tirzepatide组中体重减轻5%及以上的受试者百分比分别为85%、89%和91%，均显著高于安慰剂组的35%；10 mg和15 mg tirzepatide组中体重减轻20%及以上的受试者百分比分别50%和57%，均显著高于安慰剂组的3%。

在所有预先指定的心脏代谢指标中，Tirzepatide组均有所改善。最常见的不良反应是胃肠道反应，大多数为轻度至中度，主要发生在剂量增加期间。不良事件分别导致5 mg、10 mg和15 mg tirzepatide组与安慰剂组中4.3%、7.1%、6.2%和2.6%的受试者停止治疗。

研究结果表明，在这项为期72周的肥胖症患者试验中，每周服用5 mg、10 mg和15 mg tirzepatide，可显著且持续地减轻体重。

附：英文原文

Title: Tirzepatide Once Weekly for the Treatment of Obesity | NEJM

Author: Ania M. Jastreboff, M.D., Ph.D.,, Louis J. Aronne, M.D.,, Nadia N. Ahmad, M.D., M.P.H.,, Sean Wharton, M.D., Pharm.D.,, Lisa Connery, M.D.,, Breno Alves, M.D.,, Arihiro Kiyosue, M.D., Ph.D.,, Shuyu Zhang, M.S.,, Bing Liu, Ph.D.,, Mathijs C. Bunck, M.D., Ph.D.,, and Adam Stefanski, M.D., Ph.D.

Issue&Volume: 2022-06-04

Abstract:

Background

Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.

Methods

In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population.

Results

At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was 15.0% (95% confidence interval [CI], 15.9 to 14.2) with 5-mg weekly doses of tirzepatide, 19.5% (95% CI, 20.4 to 18.5) with 10-mg doses, and 20.9% (95% CI, 21.8 to 19.9) with 15-mg doses and 3.1% (95% CI, 4.3 to 1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.

Conclusions

In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight.

DOI: 10.1056/NEJMoa2206038

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038