The Effect of Cagrilintide and Semaglutide Combination Treatment Compared to a Weight-loss Inducing Diet on Energy Metabolism in Persons Living With Obesity: an Open-label Randomised Study

In this study we will be looking into how CagriSema influences metabolism (the process by which food is used to supply energy for the body) compared to a diet. CagriSema is a new investigational medicine. CagriSema cannot yet be prescribed by doctors but has previously been tested in humans. The study is split into 2 parts. In the first part of the study, participants will either get CagriSema or a weight loss diet (calorie reduced). In the second part of the study,all participants will get CagriSema. Which treatment participants get in the first part of the study is decided by chance. Like all medicines, the study medicine may have side effects. The study will last for about 1.5 years.

开始日期2025-09-16

申办/合作机构

Novo Nordisk A/S

NCT07011667

/ Active, not recruiting临床3期

Efficacy and Safety of Cagrilintide s.c. in Combination With Semaglutide s.c. (CagriSema s.c.) Once Weekly for Weight Management and Long-term Weight Maintenance in Participants With Obesity

This study will look at how well CagriSema helps people living with obesity to lose weight and maintain the weight loss long-term. The study has 2 parts: The first part is called 'the main study' and the second part is called 'the extension study'. In the main study participants will either get CagriSema (a study medicine) or placebo (a dummy medicine that looks like CagriSema but has no active ingredient). Which treatment participants get is decided by chance. Participants are two times more likely to get CagriSema than placebo. If participants get CagriSema in the main study, participants will continue on CagriSema in the extension study. Which dose of CagriSema participants will continue on is decided by chance. If participants get placebo in the main study, participants will get CagriSema in the extension study. Participants will take one injection of study medicine once a week. The study will last for about 3 years and 3 months.

开始日期2025-06-03

申办/合作机构

Novo Nordisk A/S

NCT06780449

/ Recruiting临床3期

Long-term Efficacy and Safety of Cagrilintide s.c. 2.4 mg in Combination With Semaglutide s.c. 2.4 mg (CagriSema 2.4 mg/2.4 mg) Once Weekly Versus Placebo in Participants With Obesity

This study will look at how well CagriSema helps people with obesity lose weight compared to a "dummy medicine". CagriSema is a new medicine developed by Novo Nordisk. CagriSema cannot yet be prescribed by doctors. The study has two parts: First part is called the main phase and will last for 2 years, and second part is called the extension phase and will last for 1 year. In the main phase participants will either get CagriSema or "dummy medicine". Which treatment participants get is decided by chance and is not known by participants or the study doctor. In the extension phase participants will get either CagriSema or slowly reduce participants dose of CagriSema if participants had CagriSema in the main phase. Which treatment participants get is decided by chance and is not known by participants or the study doctor in both phases. If participants had "dummy medicine" in the main phase, participants will get CagriSema in the extension phase. Like all medicines, the study medicine may have side effects.

开始日期2025-02-10

申办/合作机构

Novo Nordisk A/S

100 项与 Semaglutide (Novo Nordisk)/Cagrilintide 相关的临床结果

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100 项与 Semaglutide (Novo Nordisk)/Cagrilintide 相关的转化医学

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100 项与 Semaglutide (Novo Nordisk)/Cagrilintide 相关的专利（医药）

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项与 Semaglutide (Novo Nordisk)/Cagrilintide 相关的文献（医药）

2025-11-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Development of a potent Xenopus GLP-1-derived GLP-1/GIP/Y2 receptor tri-agonist for obesity and type 2 diabetes

Article

作者: Sun, Lidan ; Wang, Ting ; Gong, Binbin ; Liu, Xiyu ; Hu, Guoqiang ; Han, Jing

The drug development strategy of combining the complementary effects of different endogenous metabolism related hormones into one molecule is receiving increasing attention. In this study, we developed the unimolecular GLP-1/GIP/Y₂ receptor triple agonist, aiming to simultaneously activating the GLP-1 and GIP receptors together with the appetite-curbing Y₂ receptor to achieve better weight loss and blood glucose control. One strategy for constructing this triple agonist peptide involves coupling the GLP-1/GIP receptor dual agonist moiety with the PYY moiety through a maleimide-thiol specific reaction. Another strategy is to directly synthesize peptides with essentially identical sequences through solid-phase synthesis. Through long-acting modifications and comprehensive receptor screening, we identified a novel triple agonist, GP-38, exhibiting potent and balanced activity at GIP, GLP-1, and Y₂ receptor. In diet-induced obesity mice, GP-38 showed favourable effects on lipid metabolism, weight reduction, and glucose homeostasis with semaglutide and cagrisema used as control. Collectively, these data demonstrate that GP-38, a highly potent triple agonist targeting GLP-1, GIP, and Y₂ receptor, significantly outperforms GLP-1 receptor monotherapy in improving glucose homeostasis and reducing body weight, offers a promising pathway for the development of new treatments for obesity and type 2 diabetes.

2025-11-01·MEDICINA CLINICA

Weight management treatment in obesity

Review

作者: Rubio-Herrera, Miguel A ; Mera-Carreiro, Sara

Obesity is a chronic and relapsing disease associated with medical complications and mortality. Our improved understanding of the relevance of the gut-brain axis in regulating appetite and body weight has encouraged research into nutrient-stimulated gastroenteropancreatic hormones as a new therapeutic arsenal for the treatment of people living with obesity. Beyond the necessary lifestyle changes, this new era with second-generation drugs has been able to achieve weight loss of 15-25%, close to that of bariatric surgery. Glucagon-like peptide-1 (GLP-1) receptor agonists (RA), used as weekly injectable monotherapy or daily oral (semaglutide), achieve weight loss of 15-17%, with a good safety profile. The synergistic combination with other hormones (such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, or amylin) will allow to increase weight loss, as well as improve cardiometabolic variables. Tirzepatide (a dual GLP-1/GIP receptor agonist) achieves weight loss of up to 22.5% at the highest doses. In this same range of weight loss, it is expected that it can be achieved with the combination of Cagrisema (cagrilintide 2.4mg plus semaglutide 2.4mg), combinations of GLP-1 RAs - glucagon agonists or with the triple combination of GLP-1 RAs-GIP-Glucagon (Retatrutide). In this review, we will examine the efficacy and safety of the drugs marketed and others under ongoing clinical trials for the treatment of persons with obesity, as well as the main challenges faced by both healthcare professionals and patients in maintaining long-term treatment.

2025-08-14·NEW ENGLAND JOURNAL OF MEDICINE

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity

Article

作者: Pietiläinen, Kirsi H. ; Osorto Contreras, Cynthia Karenina ; Garvey, W. Timothy ; Zeuthen, Niels ; Rubino, Domenica ; Winning Lehmann, Eva ; Blüher, Matthias ; Davies, Melanie J. ; Wadden, Thomas ; Wilding, John P.H. ; Sbraccia, Paolo

BACKGROUND:

Semaglutide at a dose of 2.4 mg has established weight-loss and cardiovascular benefits, and cagrilintide at a dose of 2.4 mg has shown promising results in early-phase trials; the efficacy of the combination (known as CagriSema) on weight loss in persons with either overweight and coexisting conditions or obesity is unknown.

METHODS:

In a phase 3a, 68-week, multicenter, double-blind, placebo-controlled and active-controlled trial, we enrolled adults without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. Participants were randomly assigned in a ratio of 21:3:3:7 to receive the combination of semaglutide at a dose of 2.4 mg and cagrilintide at a dose of 2.4 mg, semaglutide alone at a dose of 2.4 mg, cagrilintide alone at a dose of 2.4 mg, or placebo, plus lifestyle interventions for all groups. The coprimary end points were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with cagrilintide-semaglutide as compared with placebo. Body-weight reductions of 20% or more, 25% or more, and 30% or more were assessed as confirmatory secondary end points. Effect estimates were assessed with the treatment-policy estimand (consistent with the intention-to-treat principle). Safety was assessed.

RESULTS:

A total of 3417 participants underwent randomization, with 2108 assigned to receive cagrilintide-semaglutide, 302 to receive semaglutide, 302 to receive cagrilintide, and 705 to receive placebo. The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001). Participants receiving cagrilintide-semaglutide were more likely than those receiving placebo to reach weight-loss targets of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for all comparisons). Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity.

CONCLUSIONS:

Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.).

284

项与 Semaglutide (Novo Nordisk)/Cagrilintide 相关的新闻（医药）

2025-09-16

·药事纵横

诺和诺德公布新一代胰淀素cagrilintide的3期试验的减肥效果

诺和诺德今日在2025年欧洲糖尿病研究协会（EASD）年会（9月15日至19日于奥地利维也纳举行）上，公布了3期临床试验REDEFINE 1的一项亚组分析数据。该分析旨在评估每周一次皮下注射cagrilintide 2.4 mg作为单药治疗，结合生活方式干预，对于伴有体重相关合并症但无糖尿病的肥胖或超重成年患者的有效性及安全性。 REDEFINE 1是一项为期68周的双盲、安慰剂与活性药物对照的3期临床试验，旨在评估不同治疗方案的有效性与安全性。该研究共纳入3,417名肥胖（BMI≥30 kg/m²）或超重（BMI≥27 kg/m²）且至少伴有一种肥胖相关合并症、无2型糖尿病的成年患者，比较了每周一次给药的CagriSema（cagrilintide 2.4 mg/司美格鲁肽2.4 mg复方制剂）、cagrilintide 2.4 mg单药、司美格鲁肽2.4 mg单药以及安慰剂的效果。 Cagrilintide是一种长效胰淀素类似物，可模拟天然激素胰淀素，其作用机制区别于目前已获批的GLP-1类减肥药物。在REDEFINE 1试验中，cagrilintide展现出具有临床意义的减重效果：若所有参与者坚持治疗，68周后cagrilintide组平均体重下降11.8%，安慰剂组为2.3%；约31.6%的用药组参与者体重减轻≥15%，安慰剂组该比例为4.7%。即便不考虑治疗依从性，cagrilintide组仍实现平均11.5%的体重降幅（安慰剂组3.0%），并有31.0%的参与者减重≥15%（安慰剂组5.2%）。该药物总体耐受性良好，最常见副作用为胃肠道反应，如恶心、呕吐、腹泻和便秘，这些反应多为暂时性、轻至中度；因恶心导致永久停药的患者比例在cagrilintide组为1.0%，安慰剂组为0.1%。专项3期RENEW计划将于2025年第四季度启动，旨在进一步评估cagrilintide在肥胖或超重人群中的有效性与安全性。立即扫码加入药事纵横交流群

临床3期临床结果临床成功

2025-09-16

·BioSpace

Novo’s Amylin Injectable Cagrilintide Hits 11.8% Weight Reduction in Phase III Trial

iStock, Victor Golmer The sub-analysis, presented at the European Association for the Study of Diabetes congress, showed improved safety data to counteract past tolerability issues. Novo Nordisk’s long-acting amylin analog cagrilintide reduced body weight by 11.8% after 68 weeks of treatment, according to a sub-analysis of a late-stage trial evaluating the drug. The data, presented Tuesday at the European Association for the Study of Diabetes (EASD) congress, came from the company’s REDEFINE 1 Phase III trial. This is the first time Novo has presented late-stage data for the hopeful next-generation amylin treatment as a monotherapy. The candidate “provided clinically meaningful weight loss,” according to Novo, with the 11.8% weight reduction comparing to 2.3% in patients who received a placebo, in combination with lifestyle changes. Novo touted cagrilintide as being “well-tolerated,” with just 1% of patients who received the drug discontinuing, compared to 0.1% in the placebo arm. Side effects were mostly gastrointestinal, including nausea, vomiting, diarrhea and constipation, which are all commonly reported adverse events for approved weight loss drugs. “These data highlight the exciting potential of cagrilintide to offer an alternative approach for people to lose weight, achieve health-related outcomes and manage their obesity, including a favorable tolerability profile,” Timothy Garvey, the study’s lead investigator and director of the Diabetes Research Center at the University of Alabama at Birmingham, said in a statement . The update is a step in the right direction for Novo’s candidate, which has previously been dinged by tolerability concerns in prior readouts. A previous readout from REDEFINE 1 testing CagriSema—a combination of cagrilintide and Novo’s GLP-1 agonist semaglutide—found that 12% of patients reported injection-site reaction adverse events. When patients received each drug separately, however, 2.6% of patients taking semaglutide reported the same events, compared to 17% of patients on cagrilintide, leading William Blair analysts in June to conclude that the reactions were “primarily due to the cagrilintide component” of CagriSema. Novo will evaluate cagrilintide’s safety and efficacy in people with obesity or who are overweight in a dedicated Phase III trial called RENEW, set to begin in the fourth quarter, according to Novo’s statement. Novo is, as ever, jostling with obesity market rival Eli Lilly. The rival will present further data for oral candidate orforglipron at EASD from the Phase III ATTAIN-1 trial on Wednesday. Initial results from that trial were met with shrugs when the drug failed to generate as much weight loss as injectable semaglutide, in data announced in early August. Nevertheless, Lilly is racing to get orforglipron approved as soon as possible, with the aim to beat a next-generation Novo product to market. Lilly could reportedly benefit from the use of the FDA’s newly launched Commissioner’s Priority Voucher to score a one-to-two-month review on orforglipron. However, according to Lilly, it is “ too early ” to know if the company can qualify for the voucher.

临床3期临床结果优先审批

2025-09-09

·CPHI制药在线

5.5亿美元，诺和诺德为何重金布局这一小众赛道？

关注并星标CPHI制药在线今年8月底，丹麦制药巨头诺和诺德（Novo Nordisk）宣布与Replicate Bioscience（Replicate）达成一项合作协议，双方将整合诺和诺德在心脏代谢疾病领域的治疗经验和药物开发实力，基于Replicate的自复制RNA（srRNA）平台，共同开发针对肥胖、2型糖尿病等代谢疾病的新型候选疗法。根据协议，Replicate 将有资格从诺和诺德获得高达5.5亿美元的资助，并有资格获得未来产品销售的分层版税。过去一年，这个曾靠GLP-1产品司美格鲁肽，市值一度超越奢侈品大亨LVMH的药企，正在遭受现实的价值重估。那么，诺和诺德是如何阻止逆势下滑趋势的？本次押注的srRNA技术含金量有多高？ "水逆"的诺和诺德诺和诺德和司美格鲁肽的故事，毋庸赘述。这款现象级产品，甫一上市便销售火爆，2022 年一度发生全球性短缺，持续时间超过 1 年。在这款药物的推动下，诺和诺德市值一度冲上6350亿美元。为了维持业绩持续性爆发，诺和诺德在GLP-1赛道上做深做强，从注射、口服到长效制剂，适应症也从降糖、减重延伸至心血管、抗炎、MASH等更多代谢领域。原本以为一切都可以按预想轨道发展，但去年的诺和诺德接连遭遇"水逆"。首先是连续的临床失败打击。2024年9月，诺和诺德发布旗下一款CB1反向激动剂monlunabant治疗肥胖合并代谢综合征的临床IIa期试验的初步结果：在治疗16周之后，monlunabant的3个剂量组的减重效果相比安慰剂组均有统计学显著意义上的提高；但是，减重方面似乎并没有出现剂量依赖性，也就是说monlunabant 高剂量组看到的减重效果提升有限，公司股价随即下跌近6%。 2024年底，公司的下一代减重药物CagriSema公布临床结果，该药由Cagrilintide（卡格列肽）和司美格鲁肽组成，曾被市场期待。但是临床结果显示，在68周治疗后，Cagrisema 减掉约23%的体重，比接受安慰剂治疗的患者高出约20%，比单独接受该司美格鲁肽治疗的患者高出7%。虽然减肥效果不错，但低于之前管理层给出的25%的减重效果，诺和诺德股价随即大跌17.82%。连续的试验失败，再加上礼来替尔泊肽以及新一代减重药物的步步紧逼，诺和诺德在过去一年市值大大蒸发。为了扭转困境，诺和诺德开始押注新技术。 srRNA为何接到橄榄枝？与诺和诺德达成协议的Replicate公司是一家临床阶段公司，其开创了下一代自复制RNA（srRNA）技术。srRNA与普通mRNA相比，不仅包含mRNA的基本元素：5′cap、5′UTR、3′UTR和polyA尾，还编码4个病毒非结构蛋白(nsP1-4)和一个亚基因组启动子，在体内拥有更灵活的调控能力。在saRNA序列中，编码病毒结构蛋白的基因被编码疫苗抗原的基因所取代。病毒结构蛋白的缺失使saRNA无法产生感染性病毒，因此保证了安全性。在作用机制上，与传统mRNA相比，srRNA进入人体后可实现自我复制、数量倍增。因此仅需要很低的剂量就能达到与传统mRNA相同的蛋白表达水平，同时延长体内表达时间，能够诱导更强大和持久的细胞免疫激活反应。 Replicate公司拥有一套包含多种病毒来源的合成srRNA向量库，通过选择最合适的复制酶和非结构蛋白组合，可针对不同蛋白质大小和表达需求优化载体。Replicate称，其专有技术将带来线性mRNA1000倍的表达增益、标准srRNA100倍的表达增益。另外公司不仅设计srRNA，还能优化目标蛋白的编码序列、选择合适的LNP递送体系等。目前，Replicate研发的狂犬病疫苗 RBI-4000已进入临床I期试验，且已显示出在低于其他RNA疫苗剂量下实现保护性免疫水平的成果。另一款产品RBI-1000用于一线治疗雌激素受体阳性（ER+）转移性乳腺癌的耐药突变，在临床前小鼠模型中，RBI-1000成功地引发CD4+和CD8+T细胞，导致显著的肿瘤生长抑制，并在比线状mRNA方法低100倍的剂量下，提高了生存率。除此之外，公司的管线还涵盖EB病毒预防性疫苗、自身免疫性疾病的治疗性药物等。Replicate的技术基础为诺和诺德开发长效、高效的新型代谢疾病疗法提供了坚实的技术基础。诺和诺德丰富小核酸药物技术矩阵事实上早在2021年，诺和诺德便在RNA领域有所布局，当年11月，诺和诺德以33亿美元收购RNAi（RNA干扰）技术公司Dicerna Pharmaceuticals，把Dicerna 的RNAi平台添加到其多元化的研究技术平台中。2024年3月，诺和诺德以11.1亿美元收购了Cardior Pharmaceuticals，将其核心产品CDR132L收入囊中。CDR132L是一种合成的反义寡核苷酸（ASO），旨在选择性抑制非编码RNA--miRNA-132（miR-132），调节心脏功能和病理重塑。此次收购Replicate进一步丰富了诺和诺德小核酸技术的产品矩阵。值得注意的是，srRNA技术仍在发展早期，技术壁垒相对较高、工艺开发难度大，是实实在在的小众赛道。国内目前嘉晨西海在该领域进展较快，其基于srRNA技术平台开发的带状疱疹疫苗（JCHX-105）已进入临床阶段。未来，诺和诺德能否凭借这一新型RNA疗法，开辟出新的增长路径，值得拭目以待。主要参考资料： 1、https://media.alexion.com/news-releases/news-release-details/alexion-and-dicerna-announce-collaboration-discover-and-develop. 2、https://www.biopharmadive.com/news/novo-replicate-self-amplifying-rna-obesity-research/758852/2.https://replicatebioscience.com/. 3、https://www-nature-com.libproxy1.nus.edu.sg/articles/s41467-025-55843-9. END 智药研习社近期直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床结果信使RNA

100 项与 Semaglutide (Novo Nordisk)/Cagrilintide 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床3期	美国	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	日本	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	奥地利	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	加拿大	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	德国	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	匈牙利	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	印度	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	爱尔兰	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	马来西亚	Novo Nordisk A/S	2023-02-01
2型糖尿病	临床3期	波兰	Novo Nordisk A/S	2023-02-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05394519 (REDEFINE 2, Pubmed \| N Engl J Med)	临床3期	2型糖尿病 \| 超重 \| 肥胖	1,206	Cagrilintide-Semaglutide 2.4 mg	艱獵構願顧鏇獵憲壓壓(淵淵構齋顧鑰襯醖鹹觸) = 齋積蓋蓋夢襯獵齋蓋築淵簾簾繭蓋衊獵壓構醖 (網觸蓋觸膚膚襯糧顧顧 )	积极	2025-08-14
				Placebo	艱獵構願顧鏇獵憲壓壓(淵淵構齋顧鑰襯醖鹹觸) = 繭網夢積範簾觸積遞構淵簾簾繭蓋衊獵壓構醖 (網觸蓋觸膚膚襯糧顧顧 )
NCT05394519 (REDEFINE 2, NEWS 1 \| NEWS 2 \| Pubmed \| PRNewswire) 人工标引	临床3期	超重 \| 肥胖	1,206	CagriSema	襯積製積遞醖簾簾積鏇(鬱鏇製糧顧蓋醖顧鏇鹽) = 製觸醖糧醖繭衊鹹遞蓋繭蓋選獵餘簾齋鹽壓夢 (糧顧夢廠艱獵選積繭淵 ) 更多	不佳	2025-03-10
				Placebo	襯積製積遞醖簾簾積鏇(鬱鏇製糧顧蓋醖顧鏇鹽) = 鹽襯淵構鏇鏇鑰觸鏇鬱繭蓋選獵餘簾齋鹽壓夢 (糧顧夢廠艱獵選積繭淵 ) 更多