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

The General Hospital Corp.

[+1]

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 The investigators have unpublished data from anesthetized pigs indicating a major enhancement of insulin absorption.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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8,193

项与胰高血糖素相关的文献（医药）

2025-02-01·NEUROGASTROENTEROLOGY AND MOTILITY

Dumping syndrome: Update on pathophysiology, diagnosis, and management

Review

作者: Tack, Jan ; Van de Bruaene, Cedric ; Scarpellini, Emidio ; Raymenants, Karlien

Abstract:

Background:

Dumping syndrome is a complex of gastrointestinal symptoms originally studied in peptic ulcer surgery patients. At present, it is most prevalent in patients who underwent bariatric, upper gastrointestinal cancer or anti‐reflux surgery. The symptom pattern comprises early and late dumping symptoms. Several management options have been reported including nutritional, pharmacological and surgical approaches.

Aims and Methods:

In this study, we aimed to review the current evidence on dumping syndrome definition, diagnosis and treatment, including preliminary data from newer pharmacological studies.

Results:

Current pathophysiological concepts and analyses of provocative tests has led to a clear definition of dumping syndrome, including both early and late dumping symptoms. The term postbariatric hypoglycemia represents a limited focus on late dumping only. The diagnosis relies on recognition of symptoms and signs in a patient with appropriate surgical history; and can be confirmed by provocative testing or registration of spontaneous hypoglycemia. The initial treatment focuses on dietary intervention, to which meal viscosity enhancers and/or the glycosidase inhibitor acarbose can be added. The most effective therapy is the use of short‐ or long‐acting somatostatin analogues, which is however expensive and entails side effect issues. In case of refractory hypoglycemia, diazoxide or SGLT2 inhibitors can be considered, based on limited evidence. In refractory patients, continuous enteral feeding or (rarely) surgical reinterventions have been advocated, although not supported by solid evidence. Therapies under current evaluation include the broad‐spectrum somatostatin analogue pasireotide, GLP‐1 receptor antagonists, GLP‐1 receptor agonists and administration of stable forms of glucagon are currently under study.

Conclusions:

Dumping syndrome is a well‐defined but probably under‐diagnosed complication of upper gastrointestinal, especially bariatric, and surgeries. Diagnosis is confirmed by a provocative test and incremental therapies starting with diet, adding meal viscosity enhancers or glycosidase inhibitors and adding somatostatin analogues in refractory cases. A number of emerging therapies targeting intestinal propulsion, peptide hormone effects and hypoglycemic events are under evaluation.

2025-02-01·ANTI-CANCER DRUGS

Refractory hypoglycemia is sensitive to octreotide therapy: is it triggered by sorafenib or hepatocellular carcinoma?

Article

作者: Çakmak, Mehmet ; Kiraci, Murat ; Bal, Öznur ; Topaloğlu, Oya ; Algin, Efnan ; Köş, Fahriye Tuğba

Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia through extensive tumor infiltration and the presence of insulin-like growth factor 2 precursors. In this article, a patient whose persistent hypoglycemia did not improve despite long-term intravenous glucose and high-dose steroid treatment and who was successfully treated with octreotide is described. A 50-year-old male patient with a diagnosis of metastatic HCC was admitted to the emergency department due to symptomatic hypoglycemia. His blood glucose level was found to be 40 mg/dl and he was hospitalized in our clinic for treatment. The patient, who had been on sorafenib treatment for 2 weeks due to HCC, was started on intravenous dextrose for hypoglycemia and steroid, glucagon, and octreotide treatments, respectively. The patient’s sorafenib treatment was discontinued and a second-line palliative chemotherapy was initiated. The patient responded dramatically to octreotide treatment and the need for intravenous glucose gradually decreased. Following approximately six weeks after hospitalization, the patient’s requirement for intravenous glucose was no longer necessary. HCC and its treatment is a complex process involving the activation or inhibition of various mechanisms, and refractory hypoglycemia may rarely be seen in patients with HCC. But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.

2025-01-29·JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

Persistent hypoglycemia in congenital syphilis: hyperinsulinemic hypoglycemia with a focal pancreatic lesion

Article

作者: Tunç, Gaffari ; Akyar, Mehmet ; Çağan, Eren ; Ören, Ayşe ; Guney Varal, İpek ; Denkboy Öngen, Yasemin

Abstract:

Objectives:

Congenital syphilis can cause severe morbidities such as hydrops fetalis, preterm birth, low birth weight, hepatosplenomegaly, pneumonia, hypoglycemia, etc., and mortality. Despite hypoglycemia being reported in congenital syphilis and hyperinsulinism, only one case was described. In this article, we aimed to present a newborn with congenital syphilis born to a syphilitic mother who was diagnosed with persistent hyperinsulinemic hypoglycemia with a focal lesion during follow-up.

Case presentation:

A female patient was born with a weight of 2,450 g in the 32+3rd week of pregnancy from a 30-year-old syphilitic mother who had pleural effusion and ascites, cholestasis, thrombocytopenia, and anemia at birth. Hypoglycemia was detected on the 10th day of the patient’s follow-up (47 mg/dL). The patient was unresponsive to diazoxide, and octreotide, nifedipine, and glucagon treatments were started gradually. No variants were detected in the HH gene panel, but a focal pancreatic head lesion was detected in the pancreatic head in fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography-computed tomography. Focal lesionectomy was recommended for the patient.

Conclusions:

In this article, we present a neonate with severe early congenital syphilis and focal pancreatic lesions with persistent hyperinsulinemic hypoglycemia unresponsive to diazoxide. Although hypoglycemia can be seen in congenital syphilis and has been reported before, hypoglycemia associated with hyperinsulinism is very rare; only a few patients have been presented, and a focal pancreatic lesion has not been previously reported. The pathology is unknown, but pancreatitis may cause this entity.

237

项与胰高血糖素相关的新闻（医药）

2025-01-21

·PRNewswire

The American Diabetes Association and Xeris Pharmaceuticals Announce National Collaboration to Provide Life-Saving Hypoglycemia Education and Awareness

Strategic collaboration formed to raise awareness that all people with diabetes on blood glucose-lowering medications should have glucagon, preferable a ready-to-use formulation CHICAGO and ARLINGTON, Va., Jan. 21, 2025 /PRNewswire/ -- The American Diabetes Association® (ADA) and Xeris Pharmaceuticals® (Xeris BioPharma Holdings, Inc.), a national supporter of the ADA, are pleased to announce a multi-year strategic partnership to reinforce the importance of prescribing glucagon, preferably ready-to-use, for all individuals with diabetes who are treated with insulin and/or insulin secretagogues or those at high risk of hypoglycemia (low blood glucose, also called low blood sugar), in line with the ADA's recently updated Standards of Care in Diabetes—2025 (Standards of Care).1 "Severe hypoglycemia is life-threatening, and people with diabetes on blood glucose-lowering medication are at risk for hypoglycemia. Thus, we must act with urgency to educate people about the importance of having a treatment plan in place that includes having glucagon on hand," said Charles "Chuck" Henderson, the ADA's chief executive officer. "Through this important partnership, we can save lives by ensuring individuals with diabetes who are treated with insulin have access to glucagon, preferably a ready-to-use formulation, so they can make a plan and be ready." It is estimated that up to 46% of people with type 1 diabetes and 21% of those with type 2 diabetes using insulin experience at least one severe hypoglycemia event each year.2 Hypoglycemia is conservatively responsible for more than 202,000 emergency department visits annually with approximately 25% being admitted to the hospital.3 This is unacceptable. More needs to be done to protect people at risk for severe hypoglycemia. The ADA, with support from Xeris, seeks to rectify the low rates of appropriate glucagon prescriptions by developing education materials and training resources for health care professionals and people living with diabetes, as well as through a national awareness campaign to educate people on who is at risk for severe hypoglycemia and should have glucagon, preferably ready-to-use, as a safety net. "Severe hypoglycemia is associated with up to a three-time increased risk of death in people with diabetes.4,5,6 Xeris is proud to collaborate with the ADA to urge adoption of their strengthened clinical practice recommendations around the treatment of severe hypoglycemia," said John Shannon, Xeris' CEO. "The stakes are too high for so many patients at risk to be without a safety net. Our mutual commitment is to fight for all patients living with diabetes and ensure that they can face severe low blood glucose emergencies with confidence by always having a ready-to-use glucagon on hand." To learn more about the importance of severe hypoglycemia, readiness and treatment options, visit diabetes.org/severehypo. About the American Diabetes Association The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to end diabetes and helping people thrive. For 84 years, the ADA has driven discovery and research to prevent, manage, treat, and ultimately cure diabetes. There are 136 million Americans living with diabetes or prediabetes. Through advocacy, program development, and education, we're fighting for them all. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (800-342-2383). Join the fight with us on Facebook (American Diabetes Association), Spanish Facebook (Asociación Americana de la Diabetes), LinkedIn (American Diabetes Association), and Instagram (@AmDiabetesAssn). To learn more about how we are advocating for everyone affected by diabetes, visit us on X (@AmDiabetesAssn). About Xeris Xeris (Nasdaq: XERS) is a growth-oriented biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies. Xeris has three commercially available products: Recorlev®, for the treatment of endogenous Cushing's syndrome; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia; and Keveyis®, a proven therapy for primary periodic paralysis. Xeris also has a pipeline of development programs led by XP-8121, a Phase 3-ready, once-weekly subcutaneous injection for hypothyroidism as well as multiple early-stage programs leveraging Xeris' technology platforms, XeriSol® and XeriJect®, for its partners. Xeris Biopharma Holdings is headquartered in Chicago, IL. For more information, visit , or follow us on X, LinkedIn, or Instagram. American Diabetes Association Professional Practice Committee; 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2025. Diabetes Care 1 January 2025; 48 (Supplement_1): S128–S145. Stuckey HL, Desai U, King SB, et al. The experience of a severe hypoglycaemic event from the perspective of people with diabetes and their caregivers: "What am I going to do?". Diabet Med. 2022;39(4):e14745. doi:10.1111/dme.14745 Centers for Disease Control and Prevention. National Diabetes Statistics Report. Accessed January 8, 2025. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36(5):1384-1395. doi:10.2337/dc12-2480 McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012;35(9):1897-1901. doi:10.2337/dc11-2054 Zoungas S, Patel A, Chalmers J, et al. Severe Hypoglycemia and Risks of Vascular Events and Death. N Engl J Med. 2010;363(15):1410-1418. doi: 10.1056/NEJMoa1003795. Contact: Virginia Cramer, (703) 253-4927 [email protected] SOURCE American Diabetes Association WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期

2025-01-18

·医药速览

今日《Science》: 首次发现，免疫系统控制血糖水平

当我们想到免疫系统时，通常会将其与抵抗病毒感染联系起来。然而，今天1月17日发表在《Science》题为：Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis 的文章揭示了一种叫做 2 型先天性淋巴细胞 (ILC2s) 的免疫细胞和神经元信号交流，共同调节胰高血糖素的分泌，进而控制血糖水平。当一个人禁食或高能量消耗的活动，这些活动会导致血糖水平降低。这时，身体需要启动一个精密的机制来提高血糖，将血糖水平维持在一个健康的范围内。血糖水平降低会激活肠道中的交感神经元，这些神经元会释放去甲肾上腺素，这些信号就会进入肠道内，然后和里面的免疫细胞 ILC2s 表面的肾上腺素能 β2 受体 (ADRB2) 结合。 ADRB2 信号通路激活后，ILC2s 细胞下调肠道“锚定”基因的表达，例如整合素 Itga4 和 Itgb7，以及趋化因子受体 Ccr9。这些“锚定”基因的表达减少，使得 ILC2s 细胞更容易脱离肠道组织。离开后，要去哪里呢？研究人员利用一种先进的光转换技术追踪了 ILC2s 的迁移轨迹。他们将一种名为 Kikume-Green/Red (KikGR) 的光转换蛋白引入小鼠体内，并选择性照射小肠，将肠道细胞标记为红色荧光。结果显示，禁食后，小鼠胰腺中红色荧光标记的 ILC2s 数量显著增加。这表明，禁食诱导了肠道 ILC2s 向胰腺的迁移。 ILC2s 并非随机分布在胰腺中，而是特异性地定位于胰岛内。胰岛是胰腺中分泌激素的内分泌组织，包括分泌胰高血糖素的 α 细胞。ILC2s 在胰岛中的存在表明它们可以与 α 细胞进行直接的相互作用。 ILC2s 抵达胰腺后又做了什么呢？ ILC2s 会分泌 2 型细胞因子，主要是 IL-5 和 IL-13，作用于胰岛 α 细胞上的受体（包括 Il13ra1、Il5ra 和 Csf2ra），刺激胰岛 α 细胞分泌胰高血糖素。研究人员通过体外实验发现，将从胰腺分离的 ILC2s 加入到 α 细胞培养物中后，α 细胞分泌的胰高血糖素水平显著提高，而阻断 IL-5 和 IL-13 则会抑制这一过程。此外还发现，禁食小鼠胰腺中的 ILC2s 表达高水平的 IL-5 和 IL-13。还有一个重要发现，ILC2s 迁移到胰腺的过程依赖于 ILC2s 上的肾上腺素能 β2 受体 (ADRB2)。通过基因敲除发现，敲除 ILC2s 中的 Adrb2 基因后，ILC2s 无法迁移到胰腺，导致禁食小鼠的血糖水平无法提高。还发现，在 Rag1 缺陷小鼠中，特异性敲除 ILC2s 中的 Adrb2 也会导致类似的结果。这些结果表明，ADRB2 受体是 ILC2s 迁移到胰腺的必要条件。该研究首次揭示了神经系统、免疫系统和内分泌系统之间一种未被充分认识的交互作用机制，即在低血糖情况下，肠道交感神经活性促进肠道2型先天淋巴细胞（ILC2）迁移到胰腺。ILC2产生的细胞因子刺激胰腺α细胞分泌胰高血糖素，从而促进肝脏糖异生和内源性葡萄糖生成，最终调节血糖平衡。这项研究也说明了，我们才刚刚开始掌握身体器官系统之间的通信水平。参考文献：Marko Šestan et al.,Neuronal-ILC2 interactions regulate pancreaticglucagonandglucosehomeostasis.Science387,eadi3624(2025).DOI:10.1126/science.adi3624 往期链接 “小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学 | 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普 | 医药前沿笔记 PROTAC技术 | 抗体药物 | 抗体药物偶联-ADC 核酸疫苗 | CAR技术 | 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送 ①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

临床结果

2025-01-16

·医药魔方Info

司美格鲁肽片的出现，迈过了口服多肽药物的“无人区”

1月11日，全球首个创新口服胰高糖素样肽-1受体激动剂（GLP-1RA）司美格鲁肽片在中国上市。中国糖尿病患者迎来治疗新选择——口服GLP-1RA。GLP-1被发现至今已有40多年，GLP-1药物也经历了从短效到长效、从注射到口服的迭代升级。延长半衰期的策略或许有迹可循，但突破多肽类药物的口服技术壁垒却绝非易事，诺和诺德的司美格鲁肽片作为GLP-1药物口服难题的第一个通关者便是最好的例证。启程：司美格鲁肽问世1889年，一只被切除胰腺的实验犬让科学家们知道了糖尿病的起源[1]。大约一百年后，一只实验仓鼠和一只实验大鼠的牺牲让胰高血糖素样肽-1（GLP-1）有了名字[2, 3]，科学家们随之开始探索GLP-1在治疗糖尿病上的应用。1992年，希拉毒蜥（Gila Monster）释放的一口毒液又为GLP-1成药指明了方向[4]。这便是GLP-1类药物的起源故事。2005年，在礼来和Amylin的共同努力下，第一款GLP-1药物艾塞那肽（exenatide，商品名：Byetta®）横空出世，其关键活性成分即为从希拉毒蜥毒液中分离出来的Exendin-4。不过，该药物的使用频率为每天两次。因此，诺和诺德、阿斯利康、百时美施贵宝（BMS）等公司纷纷投身研发半衰期更长的GLP-1药物。在这之中，诺和诺德脱颖而出，推出了第一款人GLP-1类似物、每天一次的GLP-1药物利拉鲁肽以及每周一次的司美格鲁肽。不过，对糖尿病患者来说，临床需求的满足远不止于疗效更好的药物，提高治疗的便捷性也是他们的需求。于是，诺和诺德决心开发司美格鲁肽口服片剂，帮助患者克服注射障碍，提升治疗依从性。入局：突破多肽口服技术壁垒多肽类药物的治疗实践可以追溯到1922年——一例14岁的1型糖尿病患者注射了胰岛素并从中获益。科学家们对口服多肽药物的探索亦始于同一时期[5, 6]，只不过，谁也没料到，这个探索过程竟如此漫长和艰难。通常来说，口服药物需要经历胃肠道吸收、进入血液循环、肝脏代谢、到达靶向部位这一系列过程后才能发挥作用，而多肽是一种极其“脆弱”的分子，第一道关卡便难以跨越。多肽本质上是一种并不稳定的蛋白质，容易在胃部的强酸环境中分解，或被消化道中的多种蛋白酶降解。此外，多肽的体积较大，难以透过细胞膜、粘液等物理屏障。这些问题就像三座大山挡在科学家面前。多肽和蛋白质药物口服吸收影响因素[7, 8]对这3个主要的递送障碍进行分析后，科学家们决定“因地制宜”解决问题。既然多肽在进入胃肠道后会遭遇强酸和蛋白酶的伏击，那就为它们打造盔甲抵御伤害，例如肠溶包衣（enteric coating）、药械组合等提供保护性的策略；若肠壁密不透风难以穿越，那便安排先遣队混入敌营制造通行缺口，例如渗透促进剂（permeation enhancer）、离子液体（ionic liquids）等增加流动性的方法。过去100多年中，以胰岛素起家的诺和诺德在蛋白质与多肽领域打造了强大的根基。诺和诺德一直以来都怀揣着一个梦想——给糖尿病患者带来口服胰岛素，实在不行，吸入剂也可以。但天不遂人愿，诺和诺德尚未找到通往口服胰岛素的正确道路。2004年，诺和诺德发现了降糖效果优异且持久的司美格鲁肽分子。考虑到GLP-1的分子量比胰岛素要小一些，诺和诺德决定全力开发口服GLP-1，但是进展也不是一帆风顺。寻找与司美格鲁肽最为适配的渗透促进剂的过程充满了挑战，难如大海捞针。时间一转眼来到了2007年3月30日这一天，专门从事药物递送研究的Emisphere公司向全世界宣布自己开发的口服递送技术可以把GLP-1做成片剂并且保留刺激胰岛素分泌的作用[9]。诺和诺德也敏锐地了解到了这一进展，不久便决定与Emisphere商谈合作。Emisphere的Eligen平台是一个包含超过1000个小分子渗透促进剂的化合物库，这些化合物以辛酸钠衍生物为主。当时，Emisphere正在利用SNAC开发肝素的口服制剂。在千万次的探索后，诺和诺德终于发现SNAC就是司美格鲁肽的最佳辅助，随后又找到了将二者制备为片剂的最佳配比，这一制剂后来被命名为NN9924（即后来的诺和忻®，境外商品名为Rybelsus®）。不过，彼时研究人员尚未摸清SNAC能够提高司美格鲁肽口服生物利用度的机制，但这并未阻碍诺和诺德对NN9924的进一步探索。冲刺：加速临床验证，全面覆盖人群2010年，诺和诺德迅速将NN9924推进临床，相继启动了该片剂的单剂量和多剂量I期临床试验[10]。这两项试验顺利完成后，诺和诺德便趁热打铁启动了一项II期概念验证研究，以评估NN9924的降糖效果。2015年，这项II期研究取得了积极的结果，NN9924的降糖效果与司美格鲁肽注射液相当[11]。第二年，满怀信心的诺和诺德启动PIONEER系列大型III期研究，进一步验证NN9924的有效性和安全性。该系列共包括12项随机对照III期临床试验，覆盖了2型糖尿病的全程管理（不同的治疗背景特征），纳入的患者数超过1万例。在接下来的两年里，诺和诺德以惊人的临床推进速度完成了9项PIONEER研究并收获了振奋人心的研究数据。与此同时，SNAC帮助司美格鲁肽实现口服递送的机制也渐渐明朗[12]。SNAC可以通过多种途径提高司美格鲁肽的口服生物利用度：①通过跨细胞转运形式促进司美格鲁肽在胃内而非肠道吸收；②通过升高局部胃黏膜pH值接近中性水平，减少胃蛋白酶对司美格鲁肽的降解；③增加细胞膜流动性以促进司美格鲁肽的跨细胞转运；④帮助维持司美格鲁肽的单体状态，增强其渗透性。基于PIONEER系列研究的积极结果，诺和诺德在2019年3月提交了NN9924的上市申请。时隔半年后，诺和诺德便惊喜地收到了FDA的批准决定，自此，NN9924一举打破了近40年来无口服GLP-1药物上市的困局。司美格鲁肽片的中国之旅中国作为世界人口大国，有着数量庞大的糖尿病患者。据统计，中国有超1.4亿糖尿病患者[13]。虽然市场已出现了SGLT-2抑制剂、DPP-4抑制剂、磺酰脲类等机制多样化的降糖药物，但是在接受治疗的患者中，仅50.1%的患者血糖控制达标[14]。为了让中国的2型糖尿病（T2D）患者也有机会拥有接受度更高的治疗选择，诺和诺德决定开展司美格鲁肽片的中国III期临床试验。2019年，两项以中国人群为主（占比75%）的III期临床试验如约启动，即PIONEER 11和PIONEER 12研究。这两项研究的设计分别与PIONEER 1和PIONEER 3研究相似，区别主要在于入组患者的地区差异。2022年12月，诺和诺德在国际糖尿病联盟（IDF）大会上公布了这两项研究的初步结果。在PIONEER 11研究中，3mg、7mg和14mg司美格鲁肽片均可显著降低中国T2D患者的HbA1c水平，其中7mg和14mg剂量组的HbA1c降幅达到了1.6%。此外，接受司美格鲁肽片剂治疗的患者，血糖达标率最高达到了85.5%。PIONEER 11研究第26周时各组HbA1c降幅及血糖达标率此外，PIONEER 11研究中，中国新诊断2型糖尿病患者单药治疗HbA1c达标率（<7.0%）最高达92.3%[15]。在PIONEER 12研究中，3mg、7mg和14mg司美格鲁肽片亦表现出显著的血糖控制效果，其中14mg剂量组中国T2D患者的HbA1c降幅同样达到了1.6%，血糖达标率达到了75.8%。PIONEER 12研究第26周时各组HbA1c降幅PIONEER 11和PIONEER 12研究的中国亚组数据充分证明了司美格鲁肽片的有效性和安全性，也为司美格鲁肽片在中国的申报及获批提供了强有力的支持。2025年1月11日，司美格鲁肽片在中国全面上市，中国糖尿病患者终于迎来口服GLP-1RA的治疗选择。总结在GLP-1第一次被报道后的30多年间，这个领域便一直是口服递送的“无人区”。无数科学家为之前赴后继但均无功而返，直到司美格鲁肽片的出现，这一困局才被正式打破。司美格鲁肽片利用渗透促进剂SNAC这种创新的口服递送技术跨越了多肽类药物难以通过胃肠道吸收的障碍，成功摘得“第一款口服GLP-1药物”的圣杯，也为糖尿病患者带来了更加便利的治疗选择。任何革命性药物的出现都离不开研究人员的不懈坚持，司美格鲁肽片正是诺和诺德用长期主义换来的突破性成果。深耕糖尿病领域百余年的诺和诺德，如今仍在为这些患者努力开发新一代治疗药物，期待诺和诺德带来的下一个突破。- 上下滑动查看参考资料 - [1] Pancreatic Extracts for the Treatment of Diabetes (1889–1914): Acomatol. American Journal of Therapeutics. 2020; 27(1):e1-e12.[2] Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature. 1983; 302(5910):716-8.[3] Glucagon-like peptide-1 7-36: a physiological incretin in man. 1987; 2(8571):1300-1304.[4] Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992; 267(11):7402-7405.[5] Oral insulin 1922–1992: the history of continuous ambition and failure. Frontiers in insulin pharmacology. 1993; pp. 144–148.[6] Oral insulin and buccal insulin: a critical reappraisal. J Diabetes Sci Technol. 2009; 3:568–584.[7] 口服多肽和蛋白质药物的研究进展. 药学进展. 2021; 45(6):452-459.[8] Advances in oral peptide therapeutics. Nature Reviews Drug Discovery. 2020; 19(4):277-289.[9] https://pipelinereview.com/index.php/2007033010705/Proteins-and-Peptides/Emisphere-Technologies-Inc.-Reports-Clinical-Data-on-Oral-Delivery-of-GLP-1-and-PYY.html[10] Emisphere 2012年财报.[11] Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2017; 318(15):1460-1470.[12] Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med. 2018; 10(467):eaar7047.[13] IDF Diabetes Atlas, 10th edn. International Diabetes Federation, 2021[14] Wang L, et al. JAMA. 2021, 326(24):2498-2506.[15] 王卫庆, 等. 中华内分泌代谢杂志. 2024;40(11):932-940.Copyright © 2025 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床结果

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

研发状态

批准上市

10 条最早获批的记录,

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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

10 条进展最快的记录,

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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	加拿大	Eli Lilly & Co.	2013-09-01
2型糖尿病	临床3期	加拿大	Eli Lilly & Co.	2013-09-01
普通感冒	临床1期	加拿大	Eli Lilly & Co.	2013-03-01

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临床结果

适应症

分期

评价

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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


ODP313 (ENDO2022)	N/A	尿崩症 copeptin	-	Glucagon (Healthy Participants)	襯製襯餘憲夢顧築膚鹹(顧襯淵餘願艱構鑰網憲) = 築鏇衊鏇窪廠選醖繭夢觸餘夢遞選鏇顧鹹憲觸 (憲齋膚獵獵憲簾鏇獵築, 2.38 ~ 28.03)	积极	2022-11-01
				Glucagon (Patients with Central Diabetes Insipidus)	襯製襯餘憲夢顧築膚鹹(顧襯淵餘願艱構鑰網憲) = 衊襯齋膚網構憲鏇築襯觸餘夢遞選鏇顧鹹憲觸 (憲齋膚獵獵憲簾鏇獵築, 0.21 ~ 1.65)
Baqsimi (ESPE2022)	N/A	HbA1c	68	Baqsimi® 3 mg	淵餘壓醖襯顧顧艱廠廠(顧蓋蓋鏇襯餘範築積淵) = 21% 淵繭廠廠鏇鏇襯遞餘憲 (衊顧構蓋範簾蓋壓窪鏇 ) 更多	积极	2022-09-15
ADA2022	N/A	-	-	Intraislet Glucagon (GCGRKOβ-cells-/-)	蓋夢選遞憲衊壓鬱製憲(醖遞蓋遞艱齋鏇選齋觸) = 構齋簾膚憲憲觸築膚顧襯遞膚積選鑰願鑰夢築 (襯淵襯廠構廠齋鑰網憲 )	-	2022-06-01
				Intraislet Glucagon (Littermate controls)	蓋夢選遞憲衊壓鬱製憲(醖遞蓋遞艱齋鏇選齋觸) = 觸築選選簾築構壓積蓋襯遞膚積選鑰願鑰夢築 (襯淵襯廠構廠齋鑰網憲 )
ADA2022	N/A	糖尿病	-	Nasal Glucagon	糧鹹鏇鹹簾壓夢鑰襯積(顧鹹範製憲網襯糧蓋築) = 網鹽鹽顧獵鹽醖鑰窪顧簾醖淵鑰築鑰鏇廠觸衊 (獵醖蓋襯選鏇艱積構網 )	-	2022-06-01
EASD2021	N/A	低血糖 type 2 diabetes	-	Nasal Glucagon (NG)	糧醖鏇餘壓鬱淵遞壓壓(鹽範齋艱蓋積積鏇網顧) = 艱膚廠製蓋醖觸夢齋餘觸鹹鹽鏇繭壓鬱製願觸 (憲齋膚製顧夢憲獵願鬱 ) 更多	积极	2021-09-30
				Liquid Stable Glucagon Rescue Pen (GRP)	糧醖鏇餘壓鬱淵遞壓壓(鹽範齋艱蓋積積鏇網顧) = 齋壓鹹觸觸衊壓鏇簾膚觸鹹鹽鏇繭壓鬱製願觸 (憲齋膚製顧夢憲獵願鬱 ) 更多
ADA2021	N/A	低血糖	-	Nasal Glucagon	鏇鏇鹽夢製齋餘選衊鹽(醖淵鬱簾範膚繭範壓築) = 構觸製鹽衊鬱醖鹽鹹醖積願夢鏇蓋鏇廠構餘壓 (鏇糧遞醖齋範衊鬱觸糧 ) 更多	-	2021-06-01
				Reconstituted Injectable Glucagon	鏇鏇鹽夢製齋餘選衊鹽(醖淵鬱簾範膚繭範壓築) = 衊醖壓淵網選糧淵鏇齋積願夢鏇蓋鏇廠構餘壓 (鏇糧遞醖齋範衊鬱觸糧 ) 更多
ADA2021	N/A	低血糖	-	Nasal Glucagon	夢齋壓遞鑰齋製選襯積(蓋憲遞壓鑰餘選願鹽顧) = 夢網餘範願觸築範鑰襯願鏇壓鬱窪餘糧衊繭製 (網襯獵鏇網憲糧淵淵觸 )	-	2021-06-01
				Liquid Stable Glucagon Rescue Pen	夢齋壓遞鑰齋製選襯積(蓋憲遞壓鑰餘選願鹽顧) = 願襯選鹽壓觸淵願願壓願鏇壓鬱窪餘糧衊繭製 (網襯獵鏇網憲糧淵淵觸 )
NCT03421379 \| NCT03339453 (EASD2020)	N/A	低血糖	-	Nasal glucagon	膚膚鏇選鑰積憲夢構蓋(遞餘壓網齋製襯鹹齋壓) = 繭繭鹽襯鑰齋構繭鑰選蓋鏇衊簾鑰艱壓鹽膚廠 (積糧簾鏇遞顧鹽築獵願 ) 更多	积极	2020-09-24
				Injectable glucagon	膚膚鏇選鑰積憲夢構蓋(遞餘壓網齋製襯鹹齋壓) = 鹹壓夢蓋構鑰襯願餘選蓋鏇衊簾鑰艱壓鹽膚廠 (積糧簾鏇遞顧鹽築獵願 ) 更多
EASD2020	N/A	-	-	Glucagon infusion	觸廠餘廠鹹廠製壓鹽醖(鬱製築鏇繭構網壓選積) = 鑰築鹽鹹積鹽構範積範獵夢廠餘夢繭繭鹽鏇顧 (鑰築淵築積顧蓋襯壓淵 ) 更多	-	2020-09-22
				Control (no glucagon)	觸廠餘廠鹹廠製壓鹽醖(鬱製築鏇繭構網壓選積) = 膚構鬱製觸糧願鬱鏇遞獵夢廠餘夢繭繭鹽鏇顧 (鑰築淵築積顧蓋襯壓淵 ) 更多