Davies Melanie J, Bajaj Harpreet S, Broholm Christa, Eliasen Astrid, Garvey W Timothy, le Roux Carel W, Lingvay Ildiko, Lyndgaard Christian Bøge, Rosenstock Julio, Pedersen Sue D
Diabetes Research Centre, University of Leicester, Leicester, United Kingdom.
NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom.
N Engl J Med. 2025 Aug 14;393(7):648-659. doi: 10.1056/NEJMoa2502082. Epub 2025 Jun 22.
Cagrilintide and semaglutide have each been shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide (called CagriSema) for weight management in adults with type 2 diabetes, including those in a subgroup who are undergoing continuous glucose monitoring.
In this phase 3a, double-blind, randomized, placebo-controlled trial conducted in 12 countries, we assigned adults with a body-mass index of 27 or more, a glycated hemoglobin level of 7 to 10%, and type 2 diabetes in a 3:1 ratio to receive once-weekly cagrilintide-semaglutide (2.4 mg each) or placebo, along with lifestyle intervention, for 68 weeks. The two primary end points were the percent change in body weight and the percentage of patients with a weight reduction of at least 5%. Additional end points were changes in glycemic measures and safety assessments. Effect estimates were calculated with the use of the treatment-policy estimand (consistent with the intention-to-treat principle).
A total of 1206 patients underwent randomization to either the cagrilintide-semaglutide group (904 patients) or the placebo group (302 patients). The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001). More patients in the cagrilintide-semaglutide group than in the placebo group had a weight reduction of 5% or more (P<0.001); the same was true of reductions of at least 10%, 15%, and 20% (P<0.001 for the last comparison). The percentage of patients who had a glycated hemoglobin level of 6.5% or less was 73.5% in the cagrilintide-semaglutide group and 15.9% in the placebo group. Gastrointestinal adverse events were reported by 72.5% of the patients in the cagrilintide-semaglutide group and 34.4% in the placebo group, most of which were transient and mild or moderate in severity.
Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes. (Funded by Novo Nordisk; REDEFINE 2 ClinicalTrials.gov number, NCT05394519.).
卡格列净肽和司美格鲁肽作为单一疗法均已显示出可诱导体重减轻。对于卡格列净肽和司美格鲁肽联合使用（称为卡格列司美）用于2型糖尿病成人患者体重管理的数据需求，包括那些正在进行持续血糖监测的亚组患者。
在这项在12个国家进行的3a期、双盲、随机、安慰剂对照试验中，我们将体重指数为27或更高、糖化血红蛋白水平为7%至10%且患有2型糖尿病的成年人按3:1的比例分配，使其接受每周一次的卡格列净肽 - 司美格鲁肽（各2.4毫克）或安慰剂，并进行生活方式干预，为期68周。两个主要终点是体重变化百分比和体重减轻至少5%的患者百分比。其他终点是血糖指标变化和安全性评估。使用治疗策略估计量（与意向性治疗原则一致）计算效应估计值。
共有1206例患者被随机分配至卡格列净肽 - 司美格鲁肽组（904例患者）或安慰剂组（302例患者）。从基线到第68周，卡格列净肽 - 司美格鲁肽组体重估计平均变化为 -13.7%，安慰剂组为 -3.4%（估计差异为 -10.4个百分点；95%置信区间为 -11.2至 -9.5；P<0.001）。卡格列净肽 - 司美格鲁肽组体重减轻5%或更多的患者比安慰剂组更多（P<0.001）；体重减轻至少10%、15%和20%的情况也是如此（最后一项比较P<0.001）。糖化血红蛋白水平为6.5%或更低的患者百分比在卡格列净肽 - 司美格鲁肽组为73.5%，在安慰剂组为15.9%。卡格列净肽 - 司美格鲁肽组72.5%的患者报告了胃肠道不良事件，安慰剂组为34.4%，其中大多数是短暂性的，严重程度为轻度或中度。
对于肥胖和2型糖尿病成人患者，每周一次的卡格列净肽 - 司美格鲁肽（各2.4毫克剂量）导致的体重显著低于安慰剂。（由诺和诺德公司资助；REDEFINE 2 临床试验注册号，NCT05394519。）
