Evaluation of PET/MR Enterography for Differentiation of Fibrotic and Inflammatory Strictures in Patients With Crohn's Disease Using a Collagen-binding Radiotracer.

In this study twenty-five (25) subjects with Crohn's disease scheduled for possible surgical intervention will be recruited for this study and a PET/MR scan using the collagen-binding radiotracer will be performed. The study aims to establish the performance figures of PET/MR using [68Ga]CBP8-PET for preoperative detection and differentiation of strictures with a fibrotic component in patients with Crohn's disease by using surgical and histologic findings (when available) as the standard for comparison. Furthermore, the investigators will determine the performance figures with which strictures are identified and characterized by PET/MR using [68Ga]CBP8-PET compared to each modality in isolation (PET alone or MR alone). Blood and tissue markers for fibrostenosis will be explored (either predictive or as biomarkers for fibrotic burden), using histologic and molecular testing by using surgical and histologic findings (when available) as the standard for comparison. Lastly the investigators want to determine the performance figures with which strictures are identified and characterized by PET/MR using [68Ga]CBP8-PET compared to each modality in isolation (PET alone or MR alone).

开始日期2023-12-19

申办/合作机构

Takeda Development Center Americas, Inc.

NCT05960565 / Recruiting临床2期IIT

Glucagon Enhanced Insulin Absorption in Diabetes Mellitus Type 1

The investigators will study the effect of microdoses of glucagon at the site of subcutaneous insulin injection. The investigators have unpublished data from anesthetized pigs indicating a major enhancement of insulin absorption.

开始日期2023-06-20

申办/合作机构

St. Olavs Hospital hf

NCT05500586 / Recruiting临床1/2期IIT

The Effects of Glucagon on Hepatic Metabolism

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

开始日期2022-10-20

申办/合作机构

Mayo Clinic

100 项与胰高血糖素相关的临床结果

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100 项与胰高血糖素相关的转化医学

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100 项与胰高血糖素相关的专利（医药）

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8,145

项与胰高血糖素相关的文献（医药）

2024-12-01·Clinical endocrinology

Paediatric perspectives in the diagnosis of polyuria‐polydipsia syndrome

Review

作者: Huynh, Tony ; Signal, Dana ; Christ‐Crain, Mirjam

Abstract:

The elucidation of the underlying cause of polyuria‐polydipsia syndrome (PPS) is a challenging—especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated‐copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population—incorporating the differences in physiological regulation of water homeostasis, and safety requirements—before there is widespread adoption into clinical practice.

2024-12-01·CELLULAR AND MOLECULAR NEUROBIOLOGY

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon

Review

作者: Alrouji, Mohammed ; Papadakis, Marios ; Al-Kuraishy, Hayder M ; Assiri, Abdullah A ; Hadi, Najah R ; Al-Gareeb, Ali I ; Batiha, Gaber El-Saber ; Welson, Nermeen N ; Ali, Naif H ; Alexiou, Athanasios

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aβ) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.

2024-11-01·Molecular Metabolism

Dietary protein defends lean mass and maintains the metabolic benefits of glucagon receptor agonism in mice

Article

作者: Tan, Tricia M.M. ; Bloom, Stephen R ; Ramos-Pittol, Jose M ; Curtis, Anna ; Murphy, Kevin G ; Lopes, Tatiana ; Hope, David C.D. ; Minnion, James S ; Sardini, Alessandro ; Shrewsbury, Jed V ; Shrewsbury, Jed ; Hope, David Cd ; Carling, David ; Tan, Tricia Mm ; Minnion, James S. ; Bewick, Gavin A ; Davies, Iona ; Dormann, Dirk ; Bewick, Gavin ; Zhou, Zijing ; Bloom, Stephen R. ; Owen, Bryn M ; Owen, Bryn M. ; Ramos-Pittol, Jose M. ; Murphy, Keving G.

OBJECTIVE:

Glucagon has long been proposed as a component of multi-agonist obesity therapeutics due to its ability to induce energy expenditure and cause weight loss. However, chronic glucagon-receptor agonism has been associated with a reduction in circulating amino acids and loss of lean mass. Importantly, it is currently not known whether the metabolic benefits of glucagon can be maintained under contexts that allow the defence of lean mass.

METHODS:

We investigate the metabolic effects of the long-acting glucagon receptor agonist, G108, when administered to obese mice at low-doses, and with dietary protein supplementation.

RESULTS:

Dietary protein supplementation can only fully defend lean mass at a low dose of G108 that is sub-anorectic and does not reduce fat mass. However, in this context, G108 is still highly effective at improving glucose tolerance and reducing liver fat in obese mice. Mechanistically, liver RNA-Seq analysis reveals that dietary protein supplementation defends anabolic processes in low-dose G108-treated mice, and its effects on treatment-relevant glucose and lipid pathways are preserved.

CONCLUSION:

Glucagon-mediated energy expenditure and weight loss may be mechanistically coupled to hypoaminocidemia and lean mass loss. However, our data suggest that glucagon can treat MAFLD at doses which allow full defence of lean mass given sufficient dietary protein intake. Therefore, proportionate glucagon therapy may be safe and effective in targeting hepatocytes and improving in glycaemia and liver fat.

232

项与胰高血糖素相关的新闻（医药）

2024-10-31

·梅斯医学

新一代“神药”？JAMA文章显示，减肥药"司美格鲁肽"，或可降低67%老年痴呆风险

最新的研究发现，最近几年流行的减肥药—司美格鲁肽，不仅能减肥，能预防自杀、能减少癌症发生、能预防成瘾性障碍，最近文章还显示，它还能降低阿尔茨海默病风险。 2024年10月24日，凯斯西储大学医学院Rong Xu教授团队在期刊 Alzheimer's & Dementia（医学一区top，13分）发表了题为：“Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US” 的研究论文，旨在评估司美格鲁肽（Semaglutide）是否具有预防阿尔茨海默病（Alzheimer disease， AD）的潜力。该研究显示，与其他抗糖尿病药（包括GLP-1R类药物）相比，用于治疗2型糖尿病（T2D）和减肥的畅销药司美格鲁肽可显著降低2型糖尿病患者患阿尔茨海默病的风险。阿尔茨海默病（Alzheimer’s disease, AD）作为老年痴呆症最常见的类型，我国约有983万患者，且目前尚无治愈方法。而在先前的研究中发现，2型糖尿病患者患阿尔茨海默病的风险更高，这可能与2型糖尿病患者的风险因素相关联。司美格鲁肽（Semaglutide）是一种胰高糖素样肽-１受体激动剂（GLP-1RA），最初被研发是用于治疗2型糖尿病的。后来大家逐渐发现，司美格鲁肽可以通过激活GLP-1受体，延缓胃排空，增加饱腹感，抑制食欲，从而带来减重的作用。 2021年6月，司美格鲁肽注射液被FDA正式批准用于肥胖或超重成人的慢性体重管理。 2024年6月，我国药品监督管理局（NMPA）批准了用于长期体重管理的司美格鲁肽注射液在中国的上市申请。事实上，司美格鲁肽的减重效果也确实令人惊喜。研究显示： --在成人2型糖尿病患者中，CagriSema（司美格鲁肽联合cagrilintide）的减重效果最好。 --在超重和肥胖的成年人中，芬特明-托吡酯和 GLP-1 受体激动剂被证明是最好的减肥药物；在 GLP-1 激动剂中，semaglutide 可能是最有效的。今天，这项真实世界研究让我们看到了司美格鲁肽新的潜力。在这项最新研究中，研究团队共纳入了1,094,761例既往未诊断为AD的符合标准的2型糖尿病（T2 DM）患者，通过模拟目标实验来比较司美格鲁肽与其他抗糖尿病药物在首次诊断AD发生风险的效果。研究团队评估了6个无AD史的不同的T2DM患者群体：包括所有患者、老年患者（≥60）、女性、男性、肥胖患者和非肥胖患者。对于每个群体，都模拟了7个目标试验，最终17,104名T2DM患者新使用司美格鲁肽，其余1,077,657名患者新使用其他降糖药物（胰岛素、二甲双胍、DDP-4i、SGLT2i、磺酰脲类药物、噻唑烷二酮，以及其他GLP-1R类药物）。在7项目标试验中，治疗策略均为在基线时开始使用司美格鲁肽或在基线时开始使用其他降糖药物，但不能同时使用。主要结局: 患者电子病历中记录的首次诊断为AD。司美格鲁肽显著降低T2D患者41%~67%AD风险研究团队发现，与使用其他7种抗糖尿病药中的任何一种相比，使用司美格鲁肽的2型糖尿病（T2D）患者患上阿尔茨海默病的风险显著降低了41%~67%。具体而言，与使用其他GLP-1RAs相比，使用司美格鲁肽的2型糖尿病（T2D）患者患上阿尔茨海默病的风险显著降低了41%，HR为0.59(0.37-0.95)；其中，司美格鲁肽与使用胰岛素相比，风险减低效果差异最大，患上阿尔茨海默病的风险降低了67%，HR为0.33(0.21-0.51)。此外，该研究还显示，在不同肥胖状态、性别和年龄组中，均观察到类似的结果。综上所述，这项研究结果首次提供了真实世界证据，支持司美格鲁肽在减轻2型糖尿病患者在阿尔茨海默病的发生和发展方面的潜在临床益处，支持进一步的临床试验来评估司美格鲁肽在延缓或预防阿尔茨海默病方面的潜力。一年内连发5篇Nature/JAMA等高分文章自2024年伊始，Rong Xu 教授团队就发布了多篇关于司美格鲁肽的研究论文，发在了Nature、JAMA等顶级期刊上。 2024年1月，Rong Xu 教授团队在 Nature Medicine （医学一区top，IF=58.7）期刊发表了题为：Association of semaglutide with risk of suicidal ideations in a real-world cohort 的研究论文。该研究显示，司美格鲁肽的使用与自杀念头的增加无关，实际上还降低了自杀念头。 2024年3月，Rong Xu 教授团队在 Molecular Psychiatry （医学一区top，IF=9.6）期刊发表了题为：Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study 的研究论文。该研究显示，司美格鲁肽与减少大麻使用障碍的发生和复发有关。 2024年5月，Rong Xu 教授团队在 Nature Communications（中科院一区top，IF=14.7）期刊发表了题为：Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population 的研究论文。这项在真实世界研究显示，司美格鲁肽与酒精使用障碍（AUD）的发生率和复发率的降低有关。 2024年7月5日，Rong Xu 教授团队在期刊JAMA Network Open （医学一区top，IF=10.5）上发表了题为：Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes 的研究论文。结果显示，在肥胖相关的13种癌症中，使用GLP-1受体激动剂（包括司美格鲁肽、利拉鲁肽）治疗的2型糖尿病患者患10种癌症的风险显著降低（包括胆囊癌、脑膜瘤、胰腺癌、肝细胞癌、卵巢癌、结直肠癌、多发性骨髓瘤、食管癌、子宫内膜癌和肾癌）。司美格鲁肽不仅在降糖，减重方面有效果，在其他方面的效果有一些有趣的结果，有网友说它要成“一代神药”了！看起来，欲望真是原罪。司美格鲁肽等这些GLP-1受体激动剂药物既然能够减少口欲，就能减少诸多疾病。来源 | 医学论文与统计分析编辑 | Swagpp ●救星！中国学者创新性开发出「阴茎增大补块」，保证阴茎的有效增粗，又安全又稳定 ●持续热议！广东一公立医院欠薪数月，停诊破产后，医生：头次听说公立也会倒闭，我们这也欠薪，会步入后尘吗？二级医院艰难处境受到关注 ●复旦大学惊人发现：仅3天的厨房烹饪油烟，就能引起肺炎和损伤肠道！持续7天更严重版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」立刻下载梅斯医学APP！

临床结果临床研究

2024-10-11

·GlobeNewswire-Health Care

Zealand Pharma provides U.S. regulatory update on dasiglucagon in congenital hyperinsulinism

Zealand Pharma provides U.S. regulatory update on dasiglucagon in congenital hyperinsulinism U.S. Food and Drug Administration (FDA) issues Complete Response Letter (CRL) for dasiglucagon in CHI for up to three weeks of dosing due to the timing of a third-party manufacturing facility reinspection The reinspection of the facility was completed in August/September 2024 for which a new inspection classification is pending Zealand remains committed to working with the FDA and the third-party manufacturer to bring dasiglucagon to patients in the U.S. as soon as possible October 9, 2024 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for Part 1 of the New Drug Application (NDA) for dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with congenital hyperinsulinism (CHI) for up to 3 weeks of dosing. The CRL is related to the timing of a reinspection at a third-party contract manufacturing facility that was completed in August/September 2024. The third-party manufacturer has not yet received its inspection classification following the reinspection. A prior inspection of the facility had identified deficiencies that did not involve dasiglucagon. These prior deficiencies had been resolved as of this reinspection. The CRL did not state any concerns about the clinical data package or safety of dasiglucagon. “We at Zealand Pharma are acutely aware of the significant unmet medical need for newborns and children with congenital hyperinsulinism who have either no or very limited treatment options today,” said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. “We are committed to working with the FDA and our third-party manufacturing partner to bring dasiglucagon to patients living with this devastating disease in the months ahead.” The regulatory review of dasiglucagon is being conducted in two parts under the same NDA. Part 1 relates to dosing of up to 3 weeks and Part 2 relates to the use beyond 3 weeks. Supporting the use of dasiglucagon in CHI beyond 3 weeks, the FDA requested additional analyses from existing continuous glucose monitoring (CGM) datasets from the Phase 3 clinical program. Zealand expects to submit these data by the end of 2024. Congenital hyperinsulinism (CHI) is a severe, ultra-rare genetic disease, primarily affecting infants and children, in which the pancreatic beta cells dysfunction and secrete too much insulin, leading to frequent, recurrent, and often severe episodes of hypoglycemia. Persistent episodes of hypoglycemia can result in seizure, brain damage and death.1,2 It is estimated that CHI develops in one out of 50,000 (or more) children, corresponding to 180-300 newborns being diagnosed with the disease in the US and Europe every year.3,4 CHI has a significant impact on patient quality of life. Complex care requirements, including continuous intravenous infusion of glucose, can result in lengthy and frequent hospitalizations and make daily social activities difficult for both patients and their families. The only currently approved medical treatment for hyperinsulinism is diazoxide, which can be associated with increased risk of fluid retention, pulmonary hypertension, and congestive heart failure.5 Glucagon and the somatostatin analog octreotide may be used but are not approved therapies. It is estimated that more than 50% of CHI patients do not respond adequately to the medical treatment options currently available, so there remains a significant unmet medical need for more and better treatment options.6 Dasiglucagon is a glucagon receptor agonist that works by causing the liver to release stored sugar to the blood and is being evaluated for the prevention and treatment of hypoglycemia in infants and children with congenital hyperinsulinism. Dasiglucagon is designed to be administered by continuous subcutaneous infusion using a wearable pump system. Zealand Pharma has a collaborative development and supply agreement with DEKA Research & Development Corporation and affiliates for the wearable subcutaneous infusion pump system. Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products. Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand’s business and activities, please visit www.zealandpharma.com. References 1) Thornton PS et al. (2015) Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children, J Pediatr. 2015;167(2):238-45. 2) Banerjee I et al. (2022) Correction to: Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families, Orphanet J Rare Dis. 2022;17:61. 3) Arnoux JB et al. (2011) Congenital hyperinsulinism: current trends in diagnosis and therapy, Orphanet J Rare Dis. 2011; 6:63. 4) Yau et al. (2020) Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389, Plos One. 2020;15(2). 5) PROGLYCEM® (diazoxide) oral suspension package insert (07/18/2024) https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/017453s024lbl.pdf (accessed October 7, 2024) 6) Yorifuji et al. (2017) Clinical practice guidelines for congenital hyperinsulinism, Clin Pediatr Endocrinol. 2017;26(3):127-152. The content above comes from the network. if any infringement, please contact us to modify.

申请上市上市批准

2024-10-11

·信达生物

【学术前沿】杨文英教授：上市在望、未来可期，盘点玛仕度肽降糖领域五项临床研究

转载自：医学界内分泌频道玛仕度肽是一类升级的双靶点[胰高糖素样肽-1（GLP-1）/胰高血糖素（GCG）双受体激动剂]降糖减重周制剂。在激动GLP-1受体实现降糖减重的基础上，玛仕度肽更进一步，通过同时激动GCG受体直接作用于肝脏并燃烧内脏脂肪，提高全身脂肪组织的能量消耗，由内而外减重并实现降糖、降压、降脂、降尿酸等全面获益，每周一次，有望一站式解决代谢患者难题。玛仕度肽作为全球研发进度最快的GLP-1/GCG双受体激动剂，已开展并完成多项临床研究，有望明年在华上市，获批降糖和减重双适应症。在近期结束的第60届欧洲糖尿病研究协会（EASD）年会上，玛仕度肽在全球超重或肥胖受试者中的16mg I 期临床研究中展现出优异的减重疗效、强劲减重速度和良好的安全性，20周减重最高达21%，并可改善超重或肥胖人群的腰围、血脂和血糖控制。其在降糖领域开展的III期临床研究——DREAMS-2研究还被评为最新突破性摘要（LBA），受到全球学者的广泛关注。 DREAMS-2主要研究者，北京医院国家老年医学中心郭立新教授：玛仕度肽临床研究者，中日友好医院杨文英教授表示： “玛仕度肽以全新和独特的作用机制发挥降糖、减重、改善代谢等多重功效，在2型糖尿病（T2DM）领域已开展了Ib期至III期的五项临床研究，其中四项均已达到主要研究终点，另一项与司美格鲁肽头对头的降糖III期临床研究（DREAMS-3）正在进行中，备受期待。多项临床研究显示，不同剂量的玛仕度肽均具有显著的降糖疗效以及良好的安全性。以玛仕度肽申请T2DM适应症上市的重要研究依据——DREAMS-1研究结果为例，玛仕度肽能有效降低糖化血红蛋白达2.15%，其耐受性良好，治疗中导致治疗中止的不良事件（TEAE）发生率较低，最常报告的胃肠道不良事件为腹泻、恶心和呕吐，程度多为轻度或中度。DREAMS-2的研究结果表明，在口服降糖药物血糖控制不佳的中国2型糖尿病患者中，玛仕度肽4mg组和6mg组治疗28周后，降糖减重的疗效显著且优于度拉糖肽1.5mg组，该结果支持玛仕度肽在口服降糖药物血糖控制不佳的中国2型糖尿病患者中的临床应用价值。玛仕度肽作为全球研究进展最快的GLP-1/GCG双受体激动剂，未来可期。除降糖效果以外，玛仕度肽的减重疗效同样显著，GLORY-1研究显示玛仕度肽能降低体重达到14.37%。此外，玛仕度肽具有全面的代谢获益，包括降低肝脏脂肪、改善血脂、血压、尿酸等多项代谢指标。那么玛仕度肽之所以能够引起国内外学者的广泛关注和兴趣，第一点是因为它是第一个GLP-1/GCG双受体激动的药物。第二点更能够看到，玛仕度肽具有良好的降糖效果和优异的减重效果，且无明显的不良反应。目前，临床中的T2DM患者超重和肥胖的比例越来越高，对于此类患者，除了需要降低糖化血红蛋白以外，也需要降低体重，同时药物的安全性也要得到保证。玛仕度肽是减重降糖疗效卓越且安全性良好的一类GLP-1/GCG双受体激动剂。此外，我们看到玛仕度肽由于其独特的作用机制，在众多的研究中显示出降糖、减重以及降低肝脏脂肪含量、改善血脂、血压等多个心血管危险因素改善的优秀效能。因此，我们期待玛仕度肽在长期使用中，除了能够降糖以外，还能够改善T2DM患者心血管代谢危险因素。这是我们非常期待的药物，因为我们在临床中非常希望有一个药物除了降低代谢指标以外对心血管危险因素也有非常好的改善作用。玛仕度肽除了激动GLP-1受体，还能够激活GCG受体，GCG受体激动后在肝脏有非常好的效应，他可以促进脂肪酸的氧化分解，改善肝脏的脂肪代谢，有望降低非酒精性脂肪肝患者的肝脏脂肪含量，改善非酒精性脂肪肝，对于2型糖尿病患者合并非酒精性脂肪肝患者有潜在价值。综上所述，玛仕度肽的临床应用颇具潜力，有望为T2DM合并超重/肥胖患者提供更为全面和有效的治疗方案。期待玛仕度肽在中国的上市，为患者带来全新的治疗选择。” 下面，本文将盘点玛仕度肽在降糖领域开展的五项临床研究，一睹玛仕度肽的疗效、安全性以及综合获益！研究周期：12周研究组别：玛仕度肽3mg、4.5mg、6mg、度拉糖肽1.5mg、安慰剂主要终点：玛仕度肽在T2DM患者中的安全性与耐受性次要终点：玛仕度肽在T2DM患者中的糖化血红蛋白（HbA1c）的变化研究结果： ➤安全性与耐受性：玛仕度肽总体安全性和耐受性良好，绝大多数治疗中出现的TEAE为短暂和轻微，最常报告的是食欲减退和胃肠道不良事件。 ➤半衰期：玛仕度肽半衰期从147.3h到673.3h（6.1天到28.1天）不等，支持每周一次给药方案。 ➤HbA1c的变化：玛仕度肽组治疗12周后HbA1c较基线平均下降1.46%至2.23%（度拉糖肽组下降1.98%，安慰剂组下降0.87%）。 ➤体重变化：玛仕度肽6mg治疗12周后体重较基线平均下降5.4%，且未达到平台期（故在II期临床研究中延长了观察时间）。该研究结果发表于Nature Communications（影响因子IF=14.7）研究周期：20周研究组别：玛仕度肽3mg、4.5mg、6mg、度拉糖肽1.5mg、安慰剂主要终点：与对照组相比，玛仕度肽连续给药20周后HbA1c较基线的变化研究结果： ➤HbA1c的变化：第20周时玛仕度肽各剂量组HbA1c平均下降1.41%至1.67%（度拉糖肽组下降1.35%，安慰剂组为0.03%），且4.5mg组和6.0mg组降糖曲线仍未达到平台期（故III期临床研究进一步延长观察时间，采用28周作为首要终点，用药剂量调整为4mg和6mg）。 ➤体重变化：第20周时玛仕度肽6mg组体重较基线平均下降7.1%，并呈剂量依赖性（度拉糖肽组体重下降2.7%，安慰剂组体重下降1.4%）。 ➤安全性和耐受性：玛仕度肽总体安全性和耐受性良好，食欲减退、恶心、呕吐、腹泻是最常报告的TEAE，严重程度主要为轻度或中度。胃肠道不良事件主要发生在给药后12周内，随着给药时间延长，胃肠道反应逐渐下降并趋于稳定。 ➤代谢方面：研究发现，玛仕度肽同时降低了腰围、血压、低密度脂蛋白胆固醇、甘油三酯、转氨酶水平等心血管代谢指标。该研究结果发表于Diabetes Care（影响因子IF=14.8） DREAMS-1研究（NCT05628311）是玛仕度肽申请获批T2DM适应症的重要依据，其为一项在中国T2DM患者中进行的III期临床研究，旨在评估饮食和运动干预后血糖控制仍不理想的患者接受玛仕度肽治疗的疗效和安全性。该研究共纳入了320例受试者，被随机分成三组，分别接受玛仕度肽4mg、6mg或安慰剂治疗，进行为期24周的双盲试验。双盲治疗期结束后，4mg和6mg剂量组继续接受相同剂量的玛仕度肽治疗，而安慰剂组转换为玛仕度肽6mg治疗，再进行24周的开放标签试验。研究的主要终点是第24周时，玛仕度肽4mg和6mg组的HbA1c相对于基线的变化。●首要终点顺利达成，玛仕度肽强效降糖，HbA1c降低2.15%基于疗效估计目标，在24周治疗期结束时，玛仕度肽4mg组和6mg组的HbA1c水平较基线分别平均下降了1.57%和2.15%，显著优于安慰剂组的0.14%（P值均＜0.0001）。玛仕度肽组的HbA1c降幅疗效维持至第48周。●关键次要终点提示玛仕度肽降糖、减重双重疗效优势治疗24周后，玛仕度肽4mg组和6mg组在减重、HbA1c达标率、体重达标率以及HbA1c与体重的复合达标率方面，均显著优于安慰剂组。治疗至第48周时，玛仕度肽6mg剂量组的体重较基线平均下降了9.6%。 ●玛仕度肽为T2DM患者带来多重心血管及肾脏代谢获益除HbA1c和体重外，玛仕度肽还降低餐后血糖、腰围、血压、血脂、转氨酶，以及尿白蛋白肌酐比等心血管及肾脏代谢指标。●安全性和耐受性良好，无额外安全性信号整体安全性与耐受性良好，与玛仕度肽既往临床研究结果一致。最常报告的不良事件是胃肠道不良事件，多为轻度或中度。无新增安全性风险。低血糖事件发生率较低，且绝大多数为1级低血糖（3.0mmol/L≤血糖<3.9mmol/L），无重度低血糖事件发生。 DREAMS-2（NCT05606913）研究在今年的第60届EASD年会上被评为最新突破性摘要（LBA），是荣登LBA榜单的4项中国研究之一，将中国声音展现于世界舞台。该研究是一项在既往接受二甲双胍联合或不联合钠-葡萄糖共转运蛋白-2抑制剂（SGLT2i）或磺酰脲类药物血糖控制不佳的中国成人T2DM患者中，评估玛仕度肽相对于度拉糖肽的疗效和安全性的随机、开放性、为期28周的III期临床研究。研究共纳入731例T2DM患者，以1:1:1的比例随机接受玛仕度肽4mg、玛仕度肽6mg或度拉糖肽1.5mg每周一次皮下给药，治疗28周。研究的主要终点为第28周时玛仕度肽4mg和6mg组与度拉糖肽1.5mg组相比HbA1c相对于基线的变化。●玛仕度肽降糖疗效强劲基于疗效估计目标，第28周时，玛仕度肽4mg组和6mg组HbA1c较基线平均降幅分别为1.69%和1.73%，均优效于度拉糖肽1.5mg组（1.38%）（P值均＜0.01）。基于疗效估计目标，第28周时，玛仕度肽4mg组和6mg组空腹血糖（FPG）水平较基线平均分别降低2.03mmol/L和2.19mmol/L，均优效于度拉糖肽1.5mg组（1.71mmol/L）（P值均＜0.05）。●玛仕度肽减重疗效显著基于疗效估计目标，第28周时，玛仕度肽4mg组和6mg组的减重疗效呈剂量依赖性，体重较基线平均降幅分别为7.13%和9.24%，均优效于度拉糖肽1.5mg组（2.86%）（P值均＜0.0001）。此外，研究结果显示，与度拉糖肽1.5mg组相比，第28周时，玛仕度肽组HbA1c<7.0%以及HbA1c≤6.5%且体重减轻≥5%和≥10%的受试者比例均显著更多。●安全性和耐受性良好，无额外安全性信号 DREAMS-2研究过程中，观察到玛仕度肽的耐受性良好，治疗中TEAE发生率较低。最常报告的胃肠道不良事件为腹泻、恶心和呕吐，程度多为轻微或中度。 DREAMS-3研究（登记号：CTR20234187）是一项在早期T2DM合并肥胖的受试者中开展的对比玛仕度肽和司美格鲁肽的有效性和安全性的III期临床研究，研究主要终点为第40周HbA1c＜7.0%且体重较基线下降≥10%的受试者比例。研究计划纳入342位受试者，目前该研究正在进行中，期待玛仕度肽的亮眼成绩。凭借强劲的降糖和减重双重优势，玛仕度肽俨然成为多个领域冉冉升起的新星，期待这一药物早日获批，为我国超重/肥胖的T2DM患者临床治疗提供强有力的新武器。专家简介杨文英教授照片已获专家知情同意主任医师、教授、博士生导师现任亚洲糖尿病学会（AASD）副主席曾任：中日友好医院内分泌代谢病中心主任、大内科主任、大内科教研室主任、医院学术委员会主任曾任中华医学会糖尿病分会主任委员，荣誉主任委员曾任《中华糖尿病杂志》创刊主编，现任荣誉主编 2012获得北京市科技进步一等奖,中华医学会科技进步二等奖 2012年度全国卫生系统先进个人，巾帼英雄等称号 2013年获亚洲糖尿病学会（AASD）首届糖尿病流行病学奖 2015年中华医学会糖尿病分会科学贡献奖 2015年获中国医师协会-医师报医学贡献专家 2017年获首届国之名医-卓越建树奖近几年已发表在国内、外核心期刊论文470余篇，如：NEJM，The Lancet diabetes& endocrinology，BMJ，Circulation，European Heart of Journal， Diabetes Care等参考文献： [1]Jiang H, et al. A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes. Nat Commun. 2022 Jun 24;13(1):3613. [2] Zhang B, et al. Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care. 2024 Jan 1;47(1):160-168. 本文旨在为医疗卫生专业人士传递更多医学信息，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，信达不推荐任何未获批的药品/适应症使用。

临床3期临床结果临床2期临床成功申请上市

100 项与胰高血糖素相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	胰高血糖素	H04AA01	DB00040

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适应症	国家/地区	公司	日期
糖尿病	加拿大	Eli Lilly Canada, Inc.	2019-09-25
低血糖	美国	Eli Lilly & Co.	1960-11-14

未上市

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适应症	最高研发状态	国家/地区	公司	日期
1型糖尿病	临床3期	美国	Eli Lilly & Co.	2013-11-01
2型糖尿病	临床1期	加拿大	Eli Lilly & Co.	2014-06-01
普通感冒	临床1期	加拿大	Eli Lilly & Co.	2013-03-01

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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


Baqsimi (ESPE2022)	N/A	HbA1c	68	Baqsimi® 3 mg	窪製糧淵襯窪膚膚窪範(鏇遞遞夢網夢遞夢蓋窪) = 21% 鏇蓋膚願鏇積廠構選鹽 (膚糧簾獵獵鏇簾繭獵艱 ) 更多	积极	2022-09-15
ADA2022	N/A	-	-	Intraislet Glucagon (GCGRKOβ-cells-/-)	獵範願顧夢醖壓蓋製鹽(糧築憲壓獵築鏇憲遞淵) = 觸顧繭醖襯蓋壓餘鏇膚衊蓋糧衊築艱鹽網蓋顧 (憲鹹鏇繭憲鏇襯襯醖壓 )	-	2022-06-01
				Intraislet Glucagon (Littermate controls)	獵範願顧夢醖壓蓋製鹽(糧築憲壓獵築鏇憲遞淵) = 築網顧糧襯顧廠觸積齋衊蓋糧衊築艱鹽網蓋顧 (憲鹹鏇繭憲鏇襯襯醖壓 )
ADA2022	N/A	糖尿病	-	Nasal Glucagon	憲醖簾積衊簾淵築繭顧(艱夢襯築顧夢網醖糧襯) = 淵廠鏇鏇衊築範觸製範範觸觸積廠艱淵衊願艱 (壓蓋襯衊選遞艱夢鬱膚 )	-	2022-06-01
EASD2021	N/A	低血糖 type 2 diabetes	-	Nasal Glucagon (NG)	構夢襯艱憲憲蓋獵簾夢(選選遞簾襯壓鬱網膚選) = 範鑰繭選夢網鹹鑰製廠鏇築廠鏇簾醖鏇襯願製 (艱衊糧憲簾齋鹹鏇積遞 ) 更多	积极	2021-09-30
				Liquid Stable Glucagon Rescue Pen (GRP)	構夢襯艱憲憲蓋獵簾夢(選選遞簾襯壓鬱網膚選) = 繭鹹艱齋艱憲窪鹹醖淵鏇築廠鏇簾醖鏇襯願製 (艱衊糧憲簾齋鹹鏇積遞 ) 更多
ADA2021	N/A	低血糖	-	Nasal Glucagon	壓膚齋艱獵膚糧齋淵膚(鹹願夢壓蓋網淵鹽壓鏇) = 膚蓋繭鹽顧醖網繭膚膚築鏇艱糧鹹顧簾構鑰餘 (範壓遞網獵壓願膚鑰繭 )	-	2021-06-01
				Liquid Stable Glucagon Rescue Pen	壓膚齋艱獵膚糧齋淵膚(鹹願夢壓蓋網淵鹽壓鏇) = 鏇範齋膚夢夢顧壓膚積築鏇艱糧鹹顧簾構鑰餘 (範壓遞網獵壓願膚鑰繭 )
ADA2021	N/A	低血糖	-	Nasal Glucagon	憲淵觸製網壓淵憲積遞(廠窪艱齋網廠築艱糧餘) = 餘獵艱醖網選築觸範積網齋繭獵醖鏇鹹鹹衊鹽 (鹹鹹積衊鏇衊夢構繭積 ) 更多	-	2021-06-01
				Reconstituted Injectable Glucagon	憲淵觸製網壓淵憲積遞(廠窪艱齋網廠築艱糧餘) = 鬱製膚壓構鹽衊遞襯築網齋繭獵醖鏇鹹鹹衊鹽 (鹹鹹積衊鏇衊夢構繭積 ) 更多
NCT03421379 \| NCT03339453 (EASD2020)	N/A	低血糖	-	Nasal glucagon	鏇願艱製簾簾憲襯製繭(憲製壓範艱齋簾選鏇齋) = 醖觸蓋觸鹽餘糧繭襯製廠鹽鑰窪選廠願獵鏇齋 (襯構襯憲築餘鬱蓋齋鑰 ) 更多	积极	2020-09-24
				Injectable glucagon	鏇願艱製簾簾憲襯製繭(憲製壓範艱齋簾選鏇齋) = 鏇蓋壓艱醖獵衊鏇膚積廠鹽鑰窪選廠願獵鏇齋 (襯構襯憲築餘鬱蓋齋鑰 ) 更多
EASD2020	N/A	-	-	Glucagon infusion	餘鏇顧觸淵壓願獵選壓(鹹廠構範襯壓製鏇醖獵) = 衊襯壓願膚鑰製範積襯鬱構膚繭顧鑰築艱鏇艱 (鏇顧鹹蓋壓窪繭鹽夢簾 ) 更多	-	2020-09-22
				Control (no glucagon)	餘鏇顧觸淵壓願獵選壓(鹹廠構範襯壓製鏇醖獵) = 願襯觸鹽鬱蓋願繭網願鬱構膚繭顧鑰築艱鏇艱 (鏇顧鹹蓋壓窪繭鹽夢簾 ) 更多
NCT03421379 (Pubmed \| Diabetes Obes Metab) 人工标引	临床3期	糖尿病	75	Glucagon Nasal Powder	廠網顧餘鹽繭鬱鏇顧繭(構糧鹹鏇構窪築廠淵廠) = 鬱淵構繭廠夢襯廠獵壓築襯壓顧網簾範醖窪廠 (憲觸鏇鬱鹹廠鏇範鏇夢 )	非劣	2020-07-01
				Glucagon Hydrochloride Solution	廠網顧餘鹽繭鬱鏇顧繭(構糧鹹鏇構窪築廠淵廠) = 鑰艱艱簾餘鹹鹽膚範壓築襯壓顧網簾範醖窪廠 (憲觸鏇鬱鹹廠鏇範鏇夢 )