Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial

IF 36.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

The Lancet Diabetes & Endocrinology Pub Date : 2026-04-17 DOI:10.1016/s2213-8587(25)00402-4

Toshimasa Yamauchi, Niels-Peter Becker, Christoffer Andersen Hagemann, Kuo-Chin Huang, Arihiro Kiyosue, Soo Lim, Yukiko Onishi, Ananda Kosuvaripalli, Tomoko Takano, Yasushi Ishigaki

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引用次数: 0

Abstract

Background

The combination of cagrilintide and semaglutide has been shown in global studies to induce reductions in bodyweight. We assessed the efficacy and safety of a fixed-dose combination of cagrilintide 2·4 mg and semaglutide 2·4 mg versus semaglutide 2·4 mg for weight management in an east Asian population.

Methods

This double-blind, parallel-group, phase 3a trial (REDEFINE 5) was conducted across 21 sites (community, hospital) in Japan and one site in Taiwan. We included participants aged at least 18 years with a BMI of at least 27 kg/m² and at least two obesity-related complications, or with a BMI of at least 35 kg/m² and at least one obesity-related complication (per the Japan Society for the Study of Obesity guidelines), with or without type 2 diabetes. Participants were randomly assigned (1:1) to once-weekly subcutaneous injections of cagrilintide–semaglutide or semaglutide (both escalated to 2·4 mg), plus lifestyle intervention, for 68 weeks. Randomisation was done centrally using an interactive web response system and stratified according to planned CT scan, BMI of at least 35 kg/m², and type 2 diabetes status. Participants, site staff, investigators, and study funder were all masked to active study treatments. The primary endpoint was relative change in bodyweight from baseline to week 68. Efficacy analyses were done in all participants who underwent randomisation, using the trial product estimand (ie, assuming the treatment was taken as intended, regardless of dose) as the primary estimand. Missing data at week 68 were imputed. Safety analyses were done in all participants who underwent randomisation and received at least one dose of trial product. This trial is registered with ClinicalTrials.gov (NCT05813925) and is complete.

Findings

Between April 3, 2023, and Sept 15, 2023, we screened 355 individuals; 331 were randomly assigned to cagrilintide–semaglutide (n=164) or semaglutide (n=167). 226 (68%) participants were male and 105 (32%) were female; 80 (24%) had type 2 diabetes. 17 (10%) participants discontinued cagrilintide–semaglutide and ten (6%) discontinued semaglutide. The estimated mean change in bodyweight from baseline to week 68 was −18·4% (SE 0·7) in the cagrilintide–semaglutide group versus −11·9% (0·7) in the semaglutide group (estimated treatment difference [ETD] −6·5 percentage points [95% CI −8·4 to −4·6]; p<0·0001). Adverse events were reported by 143 (87%) of 164 participants in the cagrilintide–semaglutide group and 141 (84%) of 167 in the semaglutide group, the most common of which were gastrointestinal disorders (87 [53%] of 164 participants in the cagrilintide–semaglutide group vs 85 [51%] of 167 in the semaglutide group). One death was reported in the semaglutide 2·4 mg group, which was not judged to be treatment related by the investigator.

Interpretation

These findings support the efficacy and safety of cagrilintide–semaglutide for weight management in individuals from east Asia with overweight or obesity, with or without type 2 diabetes.

Funding

Novo Nordisk.

Translations

For the Japanese and Mandarin translations of the abstract see Supplementary Materials section.

查看原文本刊更多论文

在日本和台湾，cagrilintide和semaglutide联合使用与单用semaglutide治疗伴有或不伴有2型糖尿病的超重或肥胖成人的疗效和安全性（re定义5）：一项多中心、随机、主动对照的3a期试验

全球研究表明，cagrilintide和semaglutide联合用药可降低体重。在东亚人群中，我们评估了cagrilintide 2.4 mg和semaglutide 2.4 mg固定剂量组合对semaglutide 2.4 mg体重管理的有效性和安全性。方法该双盲、平行组、3a期试验（redefine5）在日本的21个地点（社区、医院）和台湾的1个地点进行。我们纳入了年龄在18岁以上，BMI≥27kg /m2且至少有两种肥胖相关并发症，或BMI≥35kg /m2且至少有一种肥胖相关并发症（根据日本肥胖研究协会指南），伴有或不伴有2型糖尿病的参与者。参与者随机分配（1:1），每周皮下注射一次cagrilintide-semaglutide或semaglutide（均增加至2.4 mg），加上生活方式干预，持续68周。随机化使用交互式网络应答系统集中完成，并根据计划的CT扫描、BMI至少为35 kg/m2和2型糖尿病状况进行分层。参与者、现场工作人员、调查人员和研究资助者都接受了积极的研究治疗。主要终点是体重从基线到第68周的相对变化。对所有接受随机分组的参与者进行疗效分析，使用试验产品估计（即假设治疗按预期进行，无论剂量如何）作为主要估计。输入第68周的缺失数据。对所有接受随机分组并接受至少一剂试验产品的参与者进行了安全性分析。该试验已在ClinicalTrials.gov注册（NCT05813925），并且已经完成。在2023年4月3日至2023年9月15日期间，我们筛选了355人；331人被随机分配到cagrilintide-semaglutide组（n=164）或semaglutide组（n=167）。226人（68%）为男性，105人（32%）为女性；80人（24%）患有2型糖尿病。17名（10%）受试者停止使用cagrilintide-semaglutide， 10名（6%）受试者停止使用semaglutide。从基线到第68周，cagrilintide-semaglutide组体重的估计平均变化为- 18.4% (SE 0.7)，而semaglutide组为- 11.9% (SE 0.7)（估计治疗差异[ETD] - 6.5个百分点[95% CI - 8.4至- 4.6];p< 0.0001）。164名受试者中，cagrilintide-semaglutide组报告了143例（87%）不良事件，而167名受试者中，semaglutide组报告了141例（84%）不良事件，其中最常见的是胃肠道疾病（cagrilintide-semaglutide组164名受试者中有87例[53%]，而semaglutide组167名受试者中有85例[51%]）。西马鲁肽2.4 mg组报告1例死亡，研究者未判断其与治疗相关。这些研究结果支持cagrilintide-semaglutide用于东亚超重或肥胖患者（伴有或不伴有2型糖尿病）体重管理的有效性和安全性。FundingNovo诺。有关摘要的日文和中文翻译，请参阅补充资料部分。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

The Lancet Diabetes & Endocrinology ENDOCRINOLOGY & METABOLISM-

CiteScore

61.50

自引率

1.60%

发文量

371

期刊介绍： The Lancet Diabetes & Endocrinology, an independent journal with a global perspective and strong clinical focus, features original clinical research, expert reviews, news, and opinion pieces in each monthly issue. Covering topics like diabetes, obesity, nutrition, and more, the journal provides insights into clinical advances and practice-changing research worldwide. It welcomes original research advocating change or shedding light on clinical practice, as well as informative reviews on related topics, especially those with global health importance and relevance to low-income and middle-income countries. The journal publishes various content types, including Articles, Reviews, Comments, Correspondence, Health Policy, and Personal Views, along with Series and Commissions aiming to drive positive change in clinical practice and health policy in diabetes and endocrinology.