CagriSema versus Semaglutide 2.4 mg monotherapy for weight management in adults with overweight or obesity, with or without type 2 diabetes: a systematic review, meta-analysis, and trial sequential analysis.
完整摘要 · 中文译文
引言：司美格鲁肽2.4 mg是体重管理的参考药物治疗方案，然而许多患者未能达到理想的减重目标。CagriSema是卡格列肽与司美格鲁肽的固定剂量复方制剂，可能通过互补机制提供额外获益。我们在超重或肥胖成人（伴或不伴2型糖尿病）中，量化了其相较于司美格鲁肽2.4 mg单药治疗的增量疗效与安全性。 方法：本综述遵循PRISMA 2020（PROSPERO CRD420261380458），检索了PubMed、Embase、Cochrane CENTRAL、ScienceDirect、ClinicalTrials.gov和WHO ICTRP截至2026年6月30日的随机对照试验，比较CagriSema与司美格鲁肽2.4 mg或安慰剂。采用随机效应模型在两个预设比较组分层内合并效应，τ²采用限制性最大似然估计，并进行Hartung-Knapp-Sidik-Jonkman小样本校正，同时计算预测区间、进行留一法和限3a期试验的敏感性分析、试验序贯分析。 结果：共纳入5项试验（4746名唯一参与者）。与司美格鲁肽2.4 mg相比，CagriSema产生更大的体重下降（均数差-6.89个百分点，95% CI -8.70至-5.06；I² = 33%；预测区间-8.91至-4.86），体重绝对降幅更大（-7.16 kg，95% CI -9.15至-5.17），体重指数降幅更大（-2.41 kg/m²，95% CI -2.83至-1.99），达到20%体重降幅的可能性约为其两倍（RR 2.10，95% CI 1.78至2.47）。腰围进一步下降（-4.07 cm，95% CI -5.10至-3.04）。无增量血糖获益 （此处原文以“was detected”开头，为片段承接部分，按原文译出）……被检测到，糖化血红蛋白（-0.07，95% CI -0.14至0.01）和空腹血糖的区间完全落在预设的最小重要差异范围内。注射部位反应更为频繁（RR 3.14，95% CI 1.42至6.96）；在主要模型下，胃肠道不良事件未见显著增加（RR 1.09，95% CI 0.97至1.21）。 结论：与单用司美格鲁肽2.4 mg相比，CagriSema可产生具有临床意义的额外体重减轻，并在替代心脏代谢指标方面带来适度改善，代价是注射部位反应更频繁，且至多为适度更频繁的胃肠道事件。现有证据不足以确定两种治疗之间在严重不良事件或肿瘤方面是否存在差异，长期持久性、心血管结局和身体成分仍未确定。 系统综述注册：https://www.crd.york.ac.uk/prospero/，注册号CRD420261380458。
完整摘要 · 英文原文
INTRODUCTION: Semaglutide 2.4 mg is the reference pharmacotherapy for weight management, yet many patients do not reach ambitious weight-loss targets. CagriSema, a fixed-dose combination of cagrilintide and semaglutide, may offer additional benefit through complementary mechanisms. We quantified its incremental efficacy and safety against semaglutide 2.4 mg monotherapy in adults with overweight or obesity, with and without type 2 diabetes. METHODS: This PRISMA 2020-compliant review (PROSPERO CRD420261380458) searched PubMed, Embase, Cochrane CENTRAL, ScienceDirect, ClinicalTrials.gov and WHO ICTRP to 30 June 2026 for randomised controlled trials comparing CagriSema with semaglutide 2.4 mg or placebo. Effects were pooled within two prespecified comparator strata using random-effects models with restricted maximum likelihood estimation of τ² and a Hartung-Knapp-Sidik-Jonkman small-sample adjustment, with prediction intervals, leave-one-out and phase-3a-restricted sensitivity analyses, trial sequential analysis. RESULTS: Five trials (4,746 unique participants) were included. Versus semaglutide 2.4 mg, CagriSema produced greater weight loss (mean difference -6.89 percentage points, 95% CI -8.70 to -5.06; I² = 33%; prediction interval -8.91 to -4.86), a greater absolute reduction in body weight (-7.16 kg, 95% CI -9.15 to -5.17) and in body-mass index (-2.41 kg/m², 95% CI -2.83 to -1.99), and roughly twice the likelihood of reaching a 20% reduction (RR 2.10, 95% CI 1.78 to 2.47). Waist circumference fell further (-4.07 cm, 95% CI -5.10 to -3.04). No incremental glycaemic benefit was detected, with intervals for glycated haemoglobin (-0.07, 95% CI -0.14 to 0.01) and fasting plasma glucose lying entirely within prespecified minimal important differences. Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96); gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21). CONCLUSION: CagriSema produces clinically meaningful additional weight loss and modest improvements in surrogate cardiometabolic measures compared with semaglutide 2.4 mg alone, at the cost of more frequent injection-site reactions and, at most, modestly more frequent gastrointestinal events. The evidence is insufficient to determine whether serious adverse events or neoplasms differ between treatments, and long-term durability, cardiovascular outcomes and body composition remain undetermined. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261380458.
摘要 待译
INTRODUCTION: Semaglutide 2.4 mg is the reference pharmacotherapy for weight management, yet many patients do not reach ambitious weight-loss targets. CagriSema, a fixed-dose combination of cagrilintide and semaglutide, may offer additional benefit through complementary mechanisms. We quantified its incremental efficacy and safety against semaglutide 2.4 mg monotherapy in adults with overweight or obesity, with and without type 2 diabetes.…