近日，美国威尔康奈尔医学院Louis J. Aronne团队比较了替尔泊肽和司美格鲁肽治疗肥胖症的疗效与安全性。2025年5月11日出版的《新英格兰医学杂志》发表了这项成果。

替尔泊肽和司美格鲁肽是治疗肥胖的高效药物。与司美格鲁肽相比，替尔泊肽在肥胖但没有2型糖尿病的成年人中的疗效和安全性尚不清楚。

研究组进行了一项3b期开放标签对照试验，招募肥胖但没有2型糖尿病的成年参与者以1:1的比例随机分配，每周皮下注射一次最大耐受剂量的替尔泊肽（10mg或15mg）或最大耐受剂量的司美格鲁肽（1.7mg或2.4mg），持续72周。主要终点是从基线到第72周的体重变化百分比。关键的次要终点包括体重减轻至少10%、15%、20%和25%，以及从基线到第72周的腰围变化。

共有751名参与者接受了随机分组。在第72周，使用替尔泊肽的体重变化的最小二乘平均百分比为-20.2%（95%置信区间[CI]，-21.4至-19.1），使用司美格鲁肽的体重变化为-13.7%（95%可信区间，-14.9至-12.6）（P<0.001）。替尔泊肽和司美格鲁肽的腰围最小二乘平均变化分别为-18.4 cm（95%CI，-19.6至-17.2）和-13.0 cm（95%置信区间，-14.3至-11.7）（P<0.001）。替尔泊肽组的参与者比司美格鲁肽组的参与者更有可能体重减轻至少10%、15%、20%和25%。两个治疗组中最常见的不良事件是胃肠道不良事件，大多数严重程度为轻度至中度，主要发生在剂量递增期间。

研究结果表明，在患有肥胖但没有糖尿病的参与者中，在第72周时，在减轻体重和腰围方面，替尔泊肽的治疗优于司美格鲁肽的治疗。

附：英文原文

Title: Tirzepatide as Compared with Semaglutide for the Treatment of Obesity

Author: Louis J. Aronne, Deborah Bade Horn, Carel W. le Roux, Wayne Ho, Beverly L. Falcon, Elisa Gomez Valderas, Sagar Das, Clare J. Lee, Leonard C. Glass, Cagri Senyucel, Julia P. Dunn

Issue&Volume: 2025-05-11

Abstract:

BACKGROUND

Tirzepatide and semaglutide are highly effective medications for obesity management. The efficacy and safety of tirzepatide as compared with semaglutide in adults with obesity but without type 2 diabetes is unknown.

METHODS

In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks. The primary end point was the percent change in weight from baseline to week 72. Key secondary end points included weight reductions of at least 10%, 15%, 20%, and 25% and a change in waist circumference from baseline to week 72.

RESULTS

A total of 751 participants underwent randomization. The least-squares mean percent change in weight at week 72 was 20.2% (95% confidence interval [CI], 21.4 to 19.1) with tirzepatide and 13.7% (95% CI, 14.9 to 12.6) with semaglutide (P<0.001). The least-squares mean change in waist circumference was 18.4 cm (95% CI, 19.6 to 17.2) with tirzepatide and 13.0 cm (95% CI, 14.3 to 11.7) with semaglutide (P<0.001). Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%. The most common adverse events in both treatment groups were gastrointestinal, and most were mild to moderate in severity and occurred primarily during dose escalation.

CONCLUSIONS

Among participants with obesity but without diabetes, treatment with tirzepatide was superior to treatment with semaglutide with respect to reduction in body weight and waist circumference at week 72.

DOI: NJ202505110000005

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2416394