In this study the investigators will investigate the acute effects of increasing glucagon exposure on metabolic parameters in healthy participants.
Participants will participate in one study day. After initial baseline blood samples, a three-hour intravenous infusion with glucagon will be initiated. The infusion rate will be increased every 30 minutes.

开始日期2025-04-01

申办/合作机构

University of Copenhagen

NCT06424106

/ RecruitingN/AIIT

Effect of Glucagon on Fasting Insulin Secretion and Glucose Metabolism in Subjects Without Type 2 Diabetes

Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.

开始日期2025-04-01

申办/合作机构

Mayo Clinic

NCT06877208

/ Not yet recruitingN/A

The Effect of Glucagon on Cerebral Glucose Metabolism in Healthy Humans

This is a pilot study in which the investigators will investigate the effect of exogenous glucagon on cerebral glucose metabolism in healthy humans.
Participants will participate in either part C or part D of the study, and each participant will participate in three study days. During a study day the participant will receive an intravenous infusion of either glucagon, glucose (in an adjustable rate to match to glucose concentrations achieved with the glucagon infusion) or saline. During each study day an 18F-flouro-deoxy-glucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) scan will be performed to quantify cerebral glucose metabolism during the first part (acute effect) of the glucagon/glucose/saline infusion (part C) or the last part (later effect) of the glucagon/glucose/saline infusion (part D).

开始日期2025-03-01

申办/合作机构

University of Copenhagen

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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8,673

项与胰高血糖素相关的文献（医药）

2025-12-01·Current gastroenterology reports

Evolving Role of GLP-1 Therapies in Liver Disease

Review

作者: Jensen, Thomas ; Arndt, Gretchen ; Lindsay, Mark ; Wieland, Amanda

PURPOSE OF REVIEW:

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease. This risk paralleled the rise in obesity rates, making MASLD a consequence of the Metabolic Syndrome (MetS). Until recently, clinicians have had limited pharmaceutical options in management this disorder. Glucagon-like Peptide 1 Receptor Agonist (GLP-1 RA) treatments have emerged as potential agents for noted benefits in many aspects related to the pathology and progression of MASLD.

RECENT FINDINGS:

Numerous trials including a recent Phase 3 trial utilizing GLP-1 RA based therapies have shown benefits for improvement in MASLD including MASH and fibrosis. Molecules that also act upon the glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon have shown potential synergistic benefits in reversing inflammation and fibrosis. In summary, GLP-1 RA based therapies are being rigorously studied in management of MASLD in particular more advanced stages and likely will become foundational therapies in the future.

2025-09-01·AMERICAN JOURNAL OF PREVENTIVE MEDICINE

Geographic Disparities in Glucagon Prescriptions Across North Carolina

Article

作者: Taylor, Shawn R ; Chiyaka, Edward T ; Chaplin, Michelle D ; Drake, Evan S

INTRODUCTION:

Geographic disparities in healthcare access cause substantial difficulties for patients with diabetes, particularly in accessing emergency medicines such as glucagon. In this study, the authors examine the spatial distribution of glucagon, insulin, and sulfonylureas prescription claims for Medicaid recipients in North Carolina counties and consider how these differences affect the management of diabetes and public health policy.

METHODS:

Glucagon, insulin, and sulfonylureas claim counts in each North Carolina county as reported by the North Carolina Medicaid from January 2022 to July 2023 were used. The authors also used the medical provider density data, county classification data, and pharmacy data, all at the county level, for the state of North Carolina. The authors compared prescribing patterns across urbanicity categories using descriptive statistics and investigated spatial patterns using data visualization.

RESULTS:

Of the 100 North Carolina counties, 38% had zero glucagon claims reported, and all were rural counties. The average number of claims was higher in urban counties than in rural counties: insulin (922.2 vs 120.7), glucagon (123.7 vs 14.6), and sulfonylureas (10.0 vs 2.8). The study revealed significant disparities in diabetes care across North Carolina, with rural counties reporting the lowest glucagon, insulin, and sulfonylureas claims. Urban counties had higher healthcare provider densities and medication claims, with urban areas being 7.6 times more likely to report insulin claims than rural areas, highlighting geographic inequities in care access.

CONCLUSIONS:

By emphasizing the significance of addressing glucagon prescribing trends, this analysis recommends focused efforts to promote the equitable distribution of life-saving medicines for severe hypoglycemia.

2025-07-28·JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

The changing landscape in the evaluation of hypotonic polyuria in children and adolescents: the role of the new copeptin stimulation tests

Review

作者: Sastry, Shruti ; Garibaldi, Luigi R. ; March, Christine A. ; McPhaul, Michael J.

Abstract:

Hypotonic polyuria, also known as the polyuria-polydipsia syndrome (PPS), caused by primary polydipsia (PP), arginine vasopressin deficiency (AVP-D or central diabetes insipidus), or uncommonly by AVP resistance (AVP-R), is diagnostically challenging due to overlapping symptoms and the need to conclusively diagnose or exclude AVP-D caused by serious organic lesions of the central nervous system. Diagnostic tests that stimulate AVP secretion by increasing plasma osmolality include the water deprivation test (WDT) and the hypertonic saline test (HST). The WDT, considered the gold standard for evaluating PPS in children, has suboptimal diagnostic accuracy, is burdensome, and requires hospitalization. The HST has been used rarely in children due to safety concerns and need for intensive monitoring. The finding that some anterior pituitary stimulating agents also stimulate the posterior pituitary, and the availability of a robust serum/plasma assay for copeptin as a reliable surrogate of AVP, has allowed development of nonosmotic, copeptin/AVP stimulation tests. In the present review, we focus on these new copeptin stimulation tests, which include single stimuli with intravenous (IV) arginine, IV insulin, intramuscular glucagon, oral levodopa, and double stimuli (IV arginine-insulin or AITT; IV arginine and oral Levodopa/carbidopa or ALD-ST), which we have previously shown to induce very robust copeptin secretion. Specifically, the ALD-ST differentiated AVP-D from PP in 20 children with high diagnostic accuracy at a cutoff stimulated copeptin of 9.3 pmol/L. We propose the utilization of the outpatient ALD-ST in the early stages of PPS evaluation in children, given its safety, cost-effectiveness, and limited side effects.

225

项与胰高血糖素相关的新闻（医药）

2025-07-28

·药时代

GCG直击肝脏靶点，双管齐下“燃烧”肝脏脂肪

胰高血糖素（glucagon，GCG）作为一种经典的“分解代谢”激素，其发现至今已有100年的历史。GCG协同胰高糖素样肽-1（GLP-1）开发的双靶点、多靶点激动剂现已成为针对糖尿病、肥胖等代谢疾病治疗的重要方向。GCG受体激动在GLP-1受体激动抑制食欲的基础上，促进脂肪代谢、增加能量消耗，达到减重、降糖的双重获益。同时，GCG受体主要在肝脏表达，激活GCG受体能够抑制肝脏脂肪合成、促进脂肪酸β氧化从而燃烧肝脏脂肪，带来肝脏保护的多重受益。GCG如何调节肝脏代谢？GCG燃烧肝脏脂肪的具体机制是什么？除了燃烧肝脏脂肪以外，GCG受体激活还有哪些肝脏获益？GCG/GLP-1双受体激动剂玛仕度肽降低肝脏脂肪的具体疗效如何？带着这些问题，我们采访华中科技大学同济医学院附属同济医院余学锋教授，请他为我们解读GCG“燃烧肝脏脂肪”的具体作用机制以及GCG/GLP-1双受体激动剂改善肝脏脂肪的具体疗效。生理条件下肝脏中的脂肪是如何代谢的?余学锋教授：肝脏是机体脂质代谢的核心器官，承担了脂质的摄取与处理功能。肝脏中的脂质有2个来源3个去路。来源：肝脏中脂质的第一个来源是游离脂肪酸的摄入，摄入食物后肠道产生的乳糜微粒以及储存在脂肪组织中甘油三酯（Triglyceride，TG）分解形成的游离脂肪酸释放到血液中输送到肝脏。脂质的第二个主要来源从头脂肪生成（De novo lipogenesis，DNL）是肝细胞将食物中的碳水化合物分解产生的葡萄糖和果糖转化为脂肪酸的过程。去路：进入肝脏的脂质一部分被运输到线粒体中进行脂肪酸的β氧化，为机体提供能量，这是肝脏脂肪消耗的主要形式。肝脏脂质还可以再酯化形成甘油三酯，以脂滴的形式储存在肝细胞中。这些再酯化形成的甘油三酯少量被组装形成极低密度脂蛋白（VLDL）运输到肝脏外的血液中，剩余的脂质还累积在肝脏中。当肝脏对脂质的氧化与输出不足以消耗掉肝脏中累积的脂质就会导致肝脏脂肪变性，从而引起脂肪肝，腹型肥胖等一些列的代谢性疾病（图1）。图1 肝脏脂肪代谢示意图[1]GCG与肝脏之间有什么关系?GCG如何调节肝脏代谢呢?余学锋教授：GCG由胰腺中的胰岛α细胞分泌，在体内主要与胰岛素共同作用起到稳定血糖的作用。GCG受体主要在肝脏表达，在肝脏中发挥重要作用调节三大营养物质代谢，减少肝脏脂肪，提高肝细胞存活率。当血糖下降时，胰高血糖素会从胰腺α细胞释放到肝门静脉，从而迅速到达肝细胞与GCG受体结合、刺激腺苷酸环化酶-cAMP系统以及随后激活蛋白激酶A通路来刺激糖原分解和糖异生并刺激内源性葡萄糖生成[2]。此外，GCG受体的激活能够通过多重机制协同作用燃烧肝脏脂肪，包括抑制脏脂肪生成，促进脂肪酸氧化，增加糖异生，改善炎症、纤维化等多个方面减少肝脏脂肪含量。激动GCG受体能够直接燃烧肝脏脂肪的具体机制是什么?余学锋教授：刚刚我们也提到GCG受体激动带来的燃脂作用是多方面的，它既能够抑制脂肪合成，又能够促进脂肪分解，双管齐下，调节脂肪代谢，具体来讲：（1）GCG受体激活抑制脂肪从头合成，增强脂质耐受性。GCG受体激活介导PKA和AMPK信号，使得脂质合成途径中的关键酶乙酰辅酶a羧化酶-1和2（ACC1和ACC2）被磷酸化从而抑制其活性，能直接抑制肝内从头脂肪合成。GCG受体激活还能够抑制二甘油酯酰基转移酶DGAT和HMG-CoA还原酶，抑制甘油三酯合成并降低循环中的胆固醇水平[3]。有研究表明，静脉输注GCG可通过增加脂蛋白脂肪酶（LPL）活性加速TG从血浆中清除从而在数分钟内降低血浆TG浓度[4]。（2）GCG受体激活通过刺激脂肪分解和脂肪酸β-氧化来减少肝脏内脂质的累积。研究表明，GCG受体激活后，磷脂酶A和酰基转移酶1（Plaat1）的表达增加，非酰化脂肪酸输出显著增加，这些都表明GCG受体激活导致肝脏脂质分解代谢增加[5]。线粒体是肝细胞重要的细胞器，是肝脏中脂肪酸β氧化的场所。GCG受体激活能促进脂肪酸进入线粒体，促进脂肪β-氧化功能。同时，GCG能够增强线粒体功能从而刺激肝线粒体脂肪酸β-氧化，逆转肝脏脂肪变性。此外，GCG激活上调线粒体生物合成调节剂PGC-1α基因表达，能够加快线粒体合成，增强线粒体氧化呼吸功能[5]。综上，GCG受体激活通过多种作用机制协同作用，减少肝脏脂肪。（3）GCG激活影响多种代谢途径，减少肝脏脂肪。肝细胞中GCG受体激活刺激成纤维细胞生长因子21（FGF21）的表达和分泌增加，FGF21能够通过多种途径包括抑制脂肪生成基因的表达，增加脂肪酸的线粒体β氧化减少肝脏脂肪。此外，FGF21显著降低肝星形细胞（HSC）活化和增殖，减少Kupffer细胞和损伤肝细胞促纤维化因子的表达和分泌[6]。GCG受体激活还能够通过肝脏法尼醇X受体（FXR）路径增加能量消耗。在肝细胞中，FXR激活会抑制固醇调节元件因子结合蛋白-1c（SREBP-1c）的表达，抑制从头脂肪生成外，FXR激活还会诱导过氧化物酶体增殖激活受体（PPARα）及其靶基因的表达以促进游离脂肪酸（FFA）氧化，故FXR激活通过抑制从头脂肪生成和促进脂质氧化和清除来减少肝脏脂肪变性[7]。除了燃烧肝脏脂肪以外，GCG受体激活还有哪些肝脏获益呢?余学锋教授：GCG受体激活还能减少肝脏炎症和纤维化，提高肝细胞存活率。研究表明，在非酒精性脂肪性肝炎（NASH）的肥胖（ob）/ob小鼠模型中，与GLP-1受体激动剂相比，GCG/GLP-1双受体激动剂进一步减轻了肝纤维化和炎症。GCG/GLP-1双受体激动剂降低了血浆丙氨酸氨基转移酶（ALT）、肝脏α-平滑肌肌动蛋白、肝脏羟脯氨酸含量，免疫细胞浸润标志物CD68及纤维化评分，使用GCG/GLP-1双受体激动剂后，肝脏纤维化和炎症相关基因的转录水平显著下降，且下降幅度优于单GLP-1受体激动剂[7]。此外，在中华医学会第二十一次内分泌学学术会议（2024 CSE）上有报道公布，在胆碱缺乏的高脂肪饮食（CDHFD）建立的NASH小鼠模型中，使用GCG/GLP-1双受体激动剂玛仕度肽治疗4周，小鼠肝脏功能、肝脏脂肪变性、炎症及纤维化均得到显著改善。与NASH模型组相比，使用玛仕度肽后，小鼠肝体重比，肝脏TG，及ALT，天冬氨酸氨基转移酶（AST）均显著降低。同时HE和天狼星红染色结果显示玛仕度肽可显著改善肝脏脂肪变性，炎症反应及纤维化程度且小鼠肝脏中炎症基因与纤维化基因表达降低。GCG靶点的药物研发现状如何?余学锋教授：GCG作为一种经典的激素，其发现已经有100年的历史，GCG成药之路几经波折，从最初的拮抗剂，到如今GCG的双靶点、多靶点激动剂已成为糖尿病和肥胖等代谢领域药物开发的重要方向。其中，玛仕度肽是全球研发推进最快的GCG/GLP-1单分子双受体激动剂，近日已在我国获批上市。玛仕度肽是在人体天然激素——胃泌酸调节素（Oxyntomodulin，OXM）的基础上改造而成的，OXM本身生理性的结合并同时激活GCG受体和GLP-1受体（天然GCG和GLP-1靶点），协同作用发挥调节血糖稳态，保护β细胞功能，促进能量消耗和脂肪分解等重要作用。玛仕度肽在OXM氨基酸序列的基础上进行了改造，优化了GCG和GLP-1的激动比例，满足减重、降糖双重获益；并延长药物半衰期至10天，满足每周一次的给药方式，为减重治疗带来新的选择。GCG/GLP-1双受体激动剂玛仕度肽对于肝脏脂肪的具体疗效如何?余学锋教授：GLORY-1是玛仕度肽在中国超重肥胖（不合并糖尿病）患者中的随机、双盲、安慰剂对照的III期研究。该研究纳入610名体重指数（BMI）≥28kg/m2，或BMI≥24kg/m2且至少有一种体重相关合并症的中国成年患者。研究结果显示，4mg和6mg玛仕度肽治疗48周体重较基线下降达12%和15%。GLORY-1的探索性研究分析了玛仕度肽对中国超重/肥胖患者肝脏脂肪变性的影响，研究者使用核磁共振成像-质子密度脂肪分数（MRI-PDFF）分析了62名基线肝脏脂肪含量（LFC）≥5%的超重/肥胖且不合并糖尿病的中国成人受试者。结果显示：相较于安慰剂组，玛仕度肽4mg、6mg治疗48周，呈剂量依赖的显著减少超重或肥胖受试者的LFC达60-80%；治疗48周，玛仕度肽组的LFC正常化（LFC<5%）受试者的比例达76.0%（4mg）和77.3%（6mg）。且玛仕度肽组肝酶（ALT、AST、GGT）水平较安慰剂组明显下降[8]。专家简介余学锋教授华中科技大学同济医学院附属同济医院内分泌科主任内科学教授、主任医师、博士生导师中华医学会内分泌分会常务委员中华预防医学会健康生活方式与社区卫生专业委员会副主任委员中国医师协会内分泌代谢分会常务委员湖北省内分泌学会主任委员中华医学会内分泌分会神经与内分泌学组组长《内科急危重症杂志》副主编、《药品评价》常务编委；《临床内科杂志》、《中华糖尿病杂志》、《中国糖尿病杂志》、《中华老年多器官疾病杂志》、《华科大学报》英文版、《中国医学论坛报社》内分泌专家委员会及《糖尿病天地》编委参考文献：[1]ZHAO CL, SHANG DF, ZHOU C, et al. Clin Hepatol, 2023, 39(1): 168-174. [2]Conceição-Furber E,et al. Front Endocrinol (Lausanne)2022;13:868037.[3]Albrechtsen, NJW,et al. Diabetologia. 2023 Aug;66(8):1378-1394.[4]Galsgaard KD, Elmelund E, et al. Molecular Metabolism. 2022 Dec;66:101639. [5]Adorini, Luciano, et al. Journal of hepatology vol. 79,5 (2023): 1317-1331. [6]Tillman, Erik J, et al. Frontiers in endocrinology vol. 11 601290. 14 Dec. 2020.[7]Adorini, Luciano, et al.Journal of hepatology vol. 79,5 (2023): 1317-1331. [8]JI LN, JIANG HW, LI H, et al. Diabetes 2024;73(Supplement_1):1857-LB.GCG百年研发终成药：激活自身燃脂开关破解全球超重治疗难题2025-07-01GCG“燃脂”独特机制直击肥胖核心：脂肪过剩2025-06-15拮抗还是激动？揭开GCG靶点成药之迷2025-06-10点击这里，更多了信达生物！

2025-07-25

·EndPoints

CHMP backs Lilly’s Alzheimer’s drug in certain patients, Gilead’s twice-yearly HIV prevention shot, among others

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) landed on a number of high-profile decisions this week, including changing course on Eli Lilly’s Alzheimer’s drug in certain patients and recommending Gilead’s twice-yearly HIV preventive approach. Overall, CHMP said Friday that it is endorsing the authorization of 13 new medicines. It also said that the European Commission should reject three drugs, including Sarepta’s troubled Duchenne drug Elevidys , which Roche is licensed to distribute in Europe. Lilly’s Alzheimer’s drug Kisunla initially received a negative opinion in March. At the time, CHMP noted the benefits of the drug did not outweigh the risks of patients developing bleedings and swellings of the brain called amyloid-related imaging abnormalities (ARIA), which can be fatal. Kisunla was approved in the US in July 2024. CHMP has now reversed its previously negative opinion on Kisunla after reviewing Lilly’s new dosing plan, which includes starting off with a lower dose and additional measures to reduce the risk of ARIAs. Regulators have been wary of approving drugs with risks of ARIAs, such as Eisai and Biogen’s Alzheimer’s drug Leqembi, which was also initially rejected by the EMA last July. Since then, Leqembi was approved by the EC in April this year, becoming the first of its kind to be approved in Europe. It secured FDA approval in January. CHMP also endorsed Gilead’s twice-yearly injectable lenacapavir to prevent HIV. Lenacapavir is currently approved in Europe as a treatment for adults with multidrug-resistant HIV-1 infection, and not as a preventive measure. In a landmark move, lenacapavir was approved as PrEP in the US last month under the brand name Yeztugo. The same preventive product would have a different name in the EU : Yeytuo. Elsewhere, the European regulators also gave a positive opinion for Pfizer and BioNTech’s LP.8.1-adapted monovalent Covid-19 vaccine for individuals aged six months and older. This comes after the EMA’s Emergency Task Force recommended in May that Covid-19 vaccines need to be updated to target the LP.8.1 strain. Pfizer and BioNTech have already started manufacturing their LP.8.1-adapted Covid-19 vaccine. As soon as the EC gives its approval, the companies will be ready to ship the vaccine, they said in a Friday release . CHMP also recommended the approval of the following products: The EU regulators suggested recommending the following label expansions: CHMP recommended rejecting TETEC Tissue Engineering Technologies’ autologous cartilage-derived articular chondrocytes called Jelrix, as well as Prilenia Therapeutics’ Huntington’s disease drug Nurzigma.

上市批准疫苗

2025-07-22

·国际糖尿病idiabetes

1+1＞2！GLP-1RA联合基础胰岛素，为T2DM患者提供更优治疗选择

点击“蓝字”关注我们编者按随着2型糖尿病（T2DM）治疗策略的不断演进，早期联合治疗已经成为临床管理的重要趋势[1]。GLP-1受体激动剂（GLP-1RA）与基础胰岛素的联合使用，凭借其显著的血糖控制、体重管理以及其他获益，已被证明为一种高效且安全的治疗选择[2]。近期，荟萃分析[3]和真实世界数据[4-5]进一步支持了这一方案的优势，特别是在优化基础胰岛素的选择上，二代基础胰岛素显示出更优的疗效。我们特邀广州医科大学附属第一医院陈小燕教授分享相关研究成果，探讨这一治疗策略最新进展，为临床实践提供宝贵的循证依据。1+1＞2！GLP-1RA联合基础胰岛素为T2DM患者提供更有效选择随着临床研究的持续深入，GLP-1RA与基础胰岛素的联合治疗已逐渐成为T2DM管理中的重要治疗策略。最近，Clinical Nutrition ESPEN发表的一项系统评价与荟萃分析[3]，深入探讨了司美格鲁肽联合基础胰岛素治疗T2DM患者的疗效与安全性。该研究进一步证实，GLP-1RA与基础胰岛素的联合应用能够实现“1+1＞2”的显著疗效，展现出综合治疗的优势，为T2DM患者提供了更为有效的治疗选择。这项荟萃分析共纳入了7项随机对照试验（RCT），共2354名患者。其中司美格鲁肽组1248例，对照组1106例。所有研究均采用平行组设计，其中1项为开放标签试验。样本量范围为60~1578例，干预持续时间为3~12个月。结果显示，与安慰剂或其他治疗方法相比，司美格鲁肽与基础胰岛素联合使用可显著降低糖化血红蛋白（HbA1c）[均值差（MD）：-1.17%，P<0.00001]、体重（MD -5.99 kg，P<0.00001）和空腹血糖（FPG）（MD -1.08%，P<0.00001）。此外，联合治疗还可优化血脂代谢[包括显著降低总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL），以及显著增加高密度脂蛋白（HDL）]、减少胰岛素用量。与此同时，不增加低血糖的发生风险（RR 1.36，P=0.26）。综上，该荟萃分析表明，GLP-1RA与基础胰岛素的联合治疗在血糖控制和体重减轻方面表现出显著改善，且未增加低血糖的风险。研究结果支持在T2DM患者中使用司美格鲁肽与基础胰岛素的联合治疗。择“优”联用！二代基础胰岛素是GLP-1RA控糖不佳时的更优选择在越来越多的循证证据支持下，《胰高糖素样肽-1受体激动剂联合胰岛素治疗2型糖尿病专家共识（2025版）》[6]指出，对于口服降糖药治疗血糖控制不佳的T2DM患者可起始基础胰岛素和GLP-1RA联合治疗；同时当患者通过改变生活方式、口服降糖药和 GLP-1RA无法使血糖控制达标时，需要开始使用胰岛素，这是病情发展所需。2025版《ADA糖尿病诊疗标准》[2]同样指出，当采用GLP-1RA治疗无法达到血糖目标时，需及时添加基础胰岛素治疗。真实世界研究RESTORE-G[4-5]显示，与一代基础胰岛素相比，二代基础胰岛素联合GLP-1RA治疗效果更优。RESTORE-G研究是一项真实世界、干预性、回顾性、队列研究，纳入2011至2021年期间接受GLP-1RA±口服降糖药物治疗的T2DM患者，患者改变治疗方案，起始一代基础胰岛素或二代基础胰岛素治疗，研究设计和分组情况见下图。图. RESTORE-G研究的设计情况图. RESTORE-G研究的分组情况结果显示：GLP-1RA控制不佳后，无论是联合还是转换治疗，与一代基础胰岛素相比，二代基础胰岛素均可实现更好的血糖控制。在联合治疗中，与一代基础胰岛素相比，二代基础胰岛素均可进一步降低HbA1c（估计均值差：-0.32%，P=0.04）和FPG（-1.15 mmol/L，P=0.007）。图. GLP-1 RA控制不佳的患者，联合二代基础胰岛素可实现更好的血糖控制在转换治疗中，与一代基础胰岛素相比，二代基础胰岛素同样可进一步降低HbA1c（估计均值差：-0.22%，P=0.03）和FPG（-0.56 mmol/L，P=0.03），并且体重增加更少（-0.67 kg，P=0.04）。图. GLP-1 RA控制不佳的患者，转为二代基础胰岛素可实现更好的血糖控制与固定比例组合德谷利拉相比，GLP-1RA自由联合甘精胰岛素U300对于FPG改善更显著（-1.4 mmol/L，P=0.0003），而HbA1c改善与体重变化相似。这与自由联合方案更加灵活，不同成分滴定更充分有关。图. 与固定比例组合德谷利拉相比，GLP-1RA自由联合甘精胰岛素U300治疗，FPG改善更显著综上，该真实世界研究表明，对于GLP-1RA治疗控制不佳的T2DM患者，联合或转换基础胰岛素，尤其是二代基础胰岛素是有价值的选择。总结GLP-1RA联合基础胰岛素已被证明是一种有效的T2DM治疗方案，能够显著改善血糖控制、体重管理和血脂水平，且不增加低血糖的风险。最新的系统评价与荟萃分析显示，司美格鲁肽与基础胰岛素联合使用在多个疗效指标上优于单独使用其他治疗方案。在基础胰岛素的选择上，二代基础胰岛素具有显著优势。真实世界RESTORE-G研究表明，与一代基础胰岛素相比，联合或转换二代基础胰岛素能更有效降低HbA1c和FPG。这些研究结果表明，GLP-1RA与基础胰岛素的联合治疗，尤其是与二代基础胰岛素联用，为T2DM患者提供了更为优效的治疗方案。专家简介陈小燕教授广州医科大学附属第一医院三级主任医师、医学博士、硕士生导师、博士后合作导师广州医科大学附属第一医院内分泌科科主任南山学院内分泌模块教研室负责人第三届“羊城好医生”、“岭南名医”广州市医学会内分泌分会副主委广东省保健协会糖尿病分会主委中国民族卫生协会糖尿病分会常委广东省营养学会公共营养专委会副主委广东省保健协会甲状腺保健分会副主委广东省健康管理学会代谢与内分泌分会副主委广东省精准医学应用学会更年期健康分会副主委广东省医学会内分泌分会常委广东省药理学会内分泌代谢药理专委会副主委中国老年医学学会骨质疏松分会妇产科学专委会委员参考文献：（上下滑动查看更多）[1]中华医学会糖尿病学分会. 中国糖尿病防治指南（2024版）. 中华糖尿病杂志，2025，17(01):16-139. DOI:10.3760/cma.j.cn115791-20241203-00705.[2]American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S181-S206. doi: 10.2337/dc25-S009. PMID: 39651989; PMCID: PMC11635045.[3]Chen B, Tao L, Tian M, et al. Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis. Clin Nutr ESPEN. 2025 Apr;66:564-572. doi: 10.1016/j.clnesp.2025.01.056. Epub 2025 Jan 30. PMID: 39892787.[4]Napoli R, Nicolucci A, Larosa M, et al. Treatment intensification following glucagon-like peptide-1 receptor agonists in type 2 diabetes: Comparative effectiveness analyses between different basal insulins. RESTORE-G real-world study. Diabetes Obes Metab. 2024 Sep;26(9):3576-3586. doi: 10.1111/dom.15697. Epub 2024 Jun 10. PMID: 38853712.[5]Candido R, Nicolucci A, Larosa M, et al. Treatment intensification following glucagon-like peptide-1 receptor agonist in type 2 diabetes: Comparative effectiveness analyses between free vs. fixed combination of GLP-1 RA and basal insulin. RESTORE-G real-world study. Nutr Metab Cardiovasc Dis. 2024 Aug;34(8):1846-1853. doi: 10.1016/j.numecd.2024.03.023. Epub 2024 Mar 23. PMID: 38693036.[6]中国研究型医院学会糖尿病学专业委员会.胰高糖素样肽-1受体激动剂联合胰岛素治疗2型糖尿病专家共识(2025版)[J].中华糖尿病杂志, 2025, 17(04):421-430.DOI:10.3760/cma.j.cn115791-20241213-00729.声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等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，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。4M号: MAT-CN-2512248 版本: 1.0 审批日期: 2025年7月最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

临床结果临床2期

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
2型糖尿病	临床3期	日本	Eli Lilly & Co.	2018-02-21
1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

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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	觸淵齋蓋遞蓋鏇壓鏇選(餘繭齋壓膚製鹽鑰顧廠) = 21% 鏇蓋蓋顧製糧構壓鏇顧 (鹹繭憲構夢夢鏇窪鬱艱 ) 更多	积极	2022-09-15
NCT03970772 (Pubmed \| Diabetes Care)	N/A	1型糖尿病	17	Mini-Dose Glucagon	遞顧構顧鹹選製醖餘顧(顧構襯醖齋範獵製獵蓋) = 鹽選遞蓋鹹鏇襯壓餘範選膚鑰繭鬱淵願襯壓糧 (淵簾觸餘壓鏇製獵網簾 ) 更多	积极	2022-02-17
NCT02078726 (CTgov)	临床4期	结肠癌	100	Glucagon (Glucagon)	鏇觸醖齋窪淵網廠廠簾 = 顧製壓鬱蓋簾築製齋壓鏇鏇鹹範襯壓壓顧壓繭 (鬱範淵獵遞選積構遞壓, 餘廠廠襯遞醖衊鏇繭選 ~ 襯蓋遞鏇鏇淵網願網鏇) 更多	-	2021-04-20
				Glucagon (Placebo)	鏇觸醖齋窪淵網廠廠簾 = 選艱簾衊製願積範積襯鏇鏇鹹範襯壓壓顧壓繭 (鬱範淵獵遞選積構遞壓, 鹹範蓋積願顧鬱蓋淵窪 ~ 夢鬱齋糧蓋築築鏇鑰簾) 更多
NCT03533179 (Pubmed \| J Am Heart Assoc)	临床4期	-	10	Esmolol+Saline	範鑰膚齋築餘淵蓋餘範(衊窪鑰觸選糧積襯鹽壓) = 醖構簾襯積選願鑰願壓鹽衊簾艱願鏇鑰壓鑰壓 (衊選壓積壓齋齋鬱餘艱, 9.7 ~ 26.9) 更多	-	2020-11-03
				Esmolol+Glucagon Bolus	範鑰膚齋築餘淵蓋餘範(衊窪鑰觸選糧積襯鹽壓) = 繭簾襯廠積選簾觸淵衊鹽衊簾艱願鏇鑰壓鑰壓 (衊選壓積壓齋齋鬱餘艱, 9.7 ~ 26.9) 更多
NCT03421379 \| NCT03339453 (EASD2020)	N/A	低血糖	-	Nasal glucagon	醖襯淵鏇淵襯選鹹積醖(範簾壓艱顧憲範製顧築) = 蓋膚鑰獵淵壓蓋簾糧鏇憲範願憲鑰夢廠顧衊淵 (獵艱積選範廠糧憲鑰範 ) 更多	积极	2020-09-24
				Injectable glucagon	醖襯淵鏇淵襯選鹹積醖(範簾壓艱顧憲範製顧築) = 壓網餘構鹽膚淵選獵壓憲範願憲鑰夢廠顧衊淵 (獵艱積選範廠糧憲鑰範 ) 更多
NCT03421379 (Pubmed \| Diabetes Obes Metab) 人工标引	临床3期	糖尿病	75	Glucagon Nasal Powder	願鏇膚繭憲網獵膚鏇製(鏇網繭鑰糧鹹鹽餘網艱) = 蓋蓋餘築願遞艱簾遞構築鹽蓋壓顧獵遞製願憲 (顧鹽遞鏇夢選鹽憲簾醖 )	非劣	2020-07-01
				Glucagon Hydrochloride Solution	願鏇膚繭憲網獵膚鏇製(鏇網繭鑰糧鹹鹽餘網艱) = 鬱鑰淵廠蓋積廠糧鹽醖築鹽蓋壓顧獵遞製願憲 (顧鹽遞鏇夢選鹽憲簾醖 )
NCT02806960 (CTgov)	临床1期	2型糖尿病 \| 1型糖尿病	12	Nasal Glucagon (Treatment 1)	鬱膚製糧繭選鏇夢選醖(淵夢夢糧遞獵壓淵廠醖) = 窪窪襯衊蓋齋積鹹選簾齋鏇積簾襯襯繭餘遞壓 (襯夢鹹繭壓鹽艱醖遞齋, 築鹽鹹顧艱壓繭積襯膚 ~ 獵夢製衊鹽糧範獵顧觸) 更多	-	2019-12-13
				Nasal Glucagon (Treatment 2)	鬱膚製糧繭選鏇夢選醖(淵夢夢糧遞獵壓淵廠醖) = 鹹餘構鑰夢觸築齋簾積齋鏇積簾襯襯繭餘遞壓 (襯夢鹹繭壓鹽艱醖遞齋, 築淵鹹範簾鹹餘衊範醖 ~ 製獵蓋鏇艱餘繭積繭餘) 更多
NCT02171130 (CTgov)	临床3期	低血糖 \| 1型糖尿病	129	Nasal Glucagon	衊鬱蓋艱鏇憲糧夢築餘 = 觸夢觸夢廠蓋壓願願鹹繭鹽襯膚鑰窪壓淵鹹憲 (顧築壓範範憲鹹壓廠鹹, 獵鹹憲淵遞鹹壓艱願衊 ~ 襯構積鹽鑰淵淵製願鏇) 更多	-	2019-10-15
NCT03421379 (CTgov)	临床3期	1型糖尿病 \| 2型糖尿病 \| 低血糖 ... 更多	75	Glucagon Nasal Powder (Glucagon Nasal Powder)	範遞鹽繭齋齋壓鹹糧選 = 製鹽選餘蓋遞窪鏇壓蓋鑰遞膚襯選襯構選淵構 (壓築遞淵廠艱獵醖鏇餘, 窪鑰遞網餘壓糧構壓淵 ~ 積蓋選衊齋壓憲襯範淵) 更多	-	2019-10-08
				Glucagon Hydrochloride (Glucagon Hydrochloride Solution)	範遞鹽繭齋齋壓鹹糧選 = 網鏇廠糧膚鏇夢壓廠衊鑰遞膚襯選襯構選淵構 (壓築遞淵廠艱獵醖鏇餘, 廠壓鹽築顧構襯鏇範製 ~ 觸築積顧觸選積醖鑰壓) 更多