卡格列肽与司美格鲁肽联合对比司美格鲁肽单药治疗东亚超重或肥胖成人的3a期试验
REDEFINE 5 是一项在日本和台湾开展的双盲、随机、活性对照 3a 期试验，评估卡格列肽 2·4 mg 与司美格鲁肽 2·4 mg 固定剂量联合对比司美格鲁肽 2·4 mg 单药治疗超重或肥胖成人（伴或不伴 2 型糖尿病）的疗效与安全性。共随机 331 人，治疗 68 周。结果显示联合组体重相对变化为 -18·4%，单药组为 -11·9%，估计治疗差异 -6·5 个百分点（95% CI -8·4 至 -4·6；p<0·0001）。两组不良事件发生率相似，最常见为胃肠道疾病。
要点
- 卡格列肽联合司美格鲁肽较司美格鲁肽单药显著降低体重，估计治疗差异 -6·5 个百分点。
- 联合组体重平均下降 -18·4%，单药组下降 -11·9%，治疗 68 周。
- 两组不良事件发生率相似（87% vs 84%），最常见为胃肠道疾病。
核心结论
- 在东亚超重或肥胖成人（伴或不伴 2 型糖尿病）中，卡格列肽联合司美格鲁肽较司美格鲁肽单药显著降低体重，且安全性可接受。
研究设计与样本
- 双盲、平行组、3a 期随机对照试验（REDEFINE 5），在日本 21 个中心及台湾 1 个中心开展。
- 纳入年龄≥18 岁、BMI≥27 kg/m2 且至少 2 种肥胖相关并发症，或 BMI≥35 kg/m2 且至少 1 种肥胖相关并发症（依据日本肥胖学会指南）的成人，伴或不伴 2 型糖尿病。
- 参与者按 1:1 随机分配至每周皮下注射卡格列肽-司美格鲁肽或司美格鲁肽（均递增至 2·4 mg）联合生活方式干预，治疗 68 周。
- 共筛查 355 人，随机 331 人（联合组 164 人，单药组 167 人）；男性 226 人（68%），女性 105 人（32%）；2 型糖尿病 80 人（24%）。
- 主要终点为第 68 周体重相对基线的变化，采用试验产品估计目标进行分析。
主要发现
- 第 68 周体重相对基线估计平均变化：联合组 -18·4%（SE 0·7），单药组 -11·9%（SE 0·7）。
- 估计治疗差异为 -6·5 个百分点（95% CI -8·4 至 -4·6；p<0·0001）， favoring 联合组。
- 联合组 17 人（10%）中止治疗，单药组 10 人（6%）中止治疗。
- 不良事件发生率：联合组 143/164（87%），单药组 141/167（84%）；最常见为胃肠道疾病（联合组 87/164（53%），单药组 85/167（51%））。
- 单药组报告 1 例死亡，研究者判断与治疗无关。
关键数值与推荐
- 主要疗效终点：第 68 周体重相对基线变化，联合组 -18·4% vs 单药组 -11·9%，ETD -6·5 个百分点（95% CI -8·4 至 -4·6；p<0·0001）。
- 安全性：不良事件联合组 87%（143/164），单药组 84%（141/167）；胃肠道疾病联合组 53%（87/164），单药组 51%（85/167）。
临床怎么用
- 对于东亚超重或肥胖成人（伴或不伴 2 型糖尿病），卡格列肽与司美格鲁肽固定剂量联合可作为体重管理的强化治疗选择，较司美格鲁肽单药进一步降低体重。
- 治疗期间需关注胃肠道不良事件，联合组与单药组发生率相似。
局限性
- 研究仅纳入日本和台湾的东亚人群，结果外推至其他人群需谨慎。
- 原文未报告
- 原文未报告
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
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.
引用
- Yamauchi T, Becker NP, Hagemann CA, et al. 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. Lancet Diabetes Endocrinol. 2026. PMID: 42009015. doi:10.1016/S2213-8587(25)00402-4
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。