美国华盛顿体重管理和研究中心Domenica Rubino团队比较了持续每周皮下注射索马鲁肽与安慰剂对超重或肥胖成人体重维持的影响。2021年3月23日，该研究发表在《美国医学会杂志》上。

在超重或肥胖的人群中，继续或停止使用胰高血糖素样肽1受体激动剂索马鲁肽治疗对维持体重的影响尚不清楚。

为了比较体重超重或肥胖的成年人在每周皮下注射2.4 mg索马鲁肽持续20周后，继续治疗或改用安慰剂治疗维持体重的效果，2018年6月至2020年3月，研究组在10个国家的73个机构进行了一项随机、双盲、为期68周的临床3a期戒断研究，招募了902名体重指数至少为30（或≥27，体重相关共病≥1）且无糖尿病的成年人。在20周后，将803名参与者（89.0%）按2：1的比例随机分组，其中535例继续接受每周皮下注射索马鲁肽持续至48周，268例改用安慰剂，两组均联合生活方式干预。主要终点为体重在20周至68周的百分比变化；次要终点为腰围、收缩压和身体功能的变化。

803名参与者完成20周磨合期后平均体重减轻10.6%，平均年龄为46岁，79%为女性，平均体重为107.2千克。其中787名参与者（98.0%）完成试验，741名（92.3%）完成治疗。继续服用索马鲁肽的参与者从第20周到第68周平均体重降低了7.9%，而改用安慰剂组的参与者则增加了6.9%，差异显著。

与改用安慰剂的参与者相比，继续索马鲁肽治疗的参与者腰围减少了9.7 cm，收缩压降低了3.9 mmHg，SF-36身体功能评分改善了2.5分，差异均显著。继续索马鲁肽治疗的参与者中有49.1%报告胃肠道事件，安慰剂组中有26.1%；两组中因不良事件而停止治疗的患者比例相差不大，继续索马鲁肽组为2.4%，改用安慰剂组为2.2%。

研究结果表明，对于体重超重或肥胖的成年人，每周皮下注射2.4 mg索马鲁肽20周后，与改用安慰剂相比，索马鲁肽维持治疗48周可持续减肥。

附：英文原文

Title: Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial

Author: Domenica Rubino, Niclas Abrahamsson, Melanie Davies, Dan Hesse, Frank L. Greenway, Camilla Jensen, Ildiko Lingvay, Ofri Mosenzon, Julio Rosenstock, Miguel A. Rubio, Gottfried Rudofsky, Sayeh Tadayon, Thomas A. Wadden, Dror Dicker, STEP Investigators, Mette Friberg, Anders Sjdin, Dror Dicker, Gabriella Segal, Ofri Mosenzon, Muhammad Sabbah, Yael Sofer, Victor Vishlitzky, Eelco W. Meesters, Mirelle Serlie, Arianne van Bon, Helena Cardoso, Paula Freitas, Pedro Carneiro de Melo, Margarida Monteiro, Mariana Monteiro, Dírcea Rodrigues, Aysha Badat, Pankaj Joshi, Gulam Latiff, Essack A. Mitha, Hans H. Snyman, Elane van Nieuwenhuizen, Olga González Albarrán, Assumpta Caixas, Carmen de al Cuesta, Pedro Pablo Garcia Luna, Cristobal Morales Portillo, Pedro Mezquita Raya, Miguel Angel Rubio, Niclas Abrahamsson, Johan Hoffstedt, Fredrik von Wowern, Erik Uddman, Birgit Bach-Kliegel, Felix Beuschlein, Stefan Bilz, Alain Golay, Gottfried Rudofsky, Christopher Strey, Galyna Fadieienko, Nataliia Kosei, Tetiana Tatarchuk, Valentyna Velychko, Olesya Zinych, Stephen L. Aronoff, Harold E. Bays, Andrew P. Brockmyre, Robert S. Call, Charles Crump, Cyrus V. Desouza, Valerie Espinosa, Almena L. Free, Winston H. Gandy, Steven A. Geller, Gregory M. Gottschlich, Frank L. Greenway, Laurie Han-Conrad, Wayne Harper, Lee Herman

Issue&Volume: 2021-03-23

Abstract:

Importance  The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.

Objective  To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly.

Design, Setting, and Participants  Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes.

Interventions  A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n=535) or switched to placebo (n=268), plus lifestyle intervention in both groups.

Main Outcomes and Measures  The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]).

Results  Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was 7.9% vs +6.9% with the switch to placebo (difference, 14.8 [95% CI, 16.0 to 13.5] percentage points; P<.001). Waist circumference (9.7 cm [95% CI, 10.9 to 8.5 cm]), systolic blood pressure (3.9 mm Hg [95% CI, 5.8 to 2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P<.001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%).

Conclusions and Relevance  Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.

DOI: 10.1001/jama.2021.3224

Source: https://jamanetwork.com/journals/jama/fullarticle/2777886