更新于：2024-11-01

Diabetes Mellitus, Lipoatrophic

脂肪萎缩性糖尿病

更新于：2024-11-01

基本信息

别名

DIABETES, LIPOATROPHIC、Diabete, Lipoatrophic、Diabetes Mellitus, Lipoatrophic

+ [20]

简介

A type of diabetes mellitus that is characterized by severe INSULIN RESISTANCE and LIPODYSTROPHY. The latter may be generalized, partial, acquired, or congenital (LIPODYSTROPHY, CONGENITAL GENERALIZED).

关联

项与脂肪萎缩性糖尿病相关的药物

Empagliflozin

恩格列净

靶点

SGLT2

作用机制

SGLT2抑制剂

在研机构

Eli Lilly & Co. [+10]

原研机构

Boehringer Ingelheim GmbH

在研适应症

心血管疾病 [+19]

非在研适应症

急性失代偿性心力衰竭 [+17]

最高研发阶段批准上市

首次获批国家/地区

澳大利亚

首次获批日期2014-04-30

Mecasermin

美卡舍明

靶点

IGF-1R

作用机制

IGF-1R激动剂

在研机构

Orphan Pharma International

原研机构

Astellas Pharma, Inc.

在研适应症

脂肪萎缩性糖尿病 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1994-10-05

项与脂肪萎缩性糖尿病相关的临床试验

JPRN-UMIN000043693 / Completed

Patient Experiences and Perceptions of Living with Refractory Diabetes Mellitus with Insulin Resistance in Japan -A Qualitative Research - Refractory Diabetes Mellitus with Insulin Resistance -Patient Experiences and Perceptions in Japan

开始日期2021-03-23

申办/合作机构

Nippon Boehringer Ingelheim Co., Ltd.

NCT04221152 / Unknown status临床3期

A Multicenter, Open-label, Single-arm, Extension Study With Regard to the Safety and Efficacy of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance (EMPIRE-02)

A multicenter, open-label, single-arm, extension study with regard to the safety and efficacy of empagliflozin in patients with refractory diabetes mellitus with insulin resistance.

开始日期2020-02-01

申办/合作机构

Kobe University

[+1]

NCT04018365 / Unknown status临床3期

A Multicenter, Open-label, Single-arm Study With Regard to the Efficacy and Safety of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance

A multicenter, open-label, single-arm study with regard to the efficacy and safety of empagliflozin in patients with refractory diabetes mellitus with insulin resistance

开始日期2019-09-01

申办/合作机构

Kobe University

[+1]

100 项与脂肪萎缩性糖尿病相关的临床结果

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100 项与脂肪萎缩性糖尿病相关的转化医学

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0 项与脂肪萎缩性糖尿病相关的专利（医药）

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256

项与脂肪萎缩性糖尿病相关的文献（医药）

2024-09-01·Gene Therapy

Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy

Article

作者: Roumane, Ahlima ; Mcilroy, George D ; Rochford, Justin J ; Tiwari, Mansi ; Han, Weiping ; Delibegović, Mirela ; Sommer, Nadine

AbstractLipodystrophy is a rare disorder which can be life-threatening. Here individuals fail to develop or maintain appropriate adipose tissue stores. This typically causes severe metabolic complications, including hepatic steatosis and lipoatrophic diabetes. There is no cure for lipodystrophy, and treatment options remain very limited. Here we evaluate whether tissue-selective adeno-associated virus (AAV) vectors can provide a targeted form of gene therapy for lipodystrophy, using a preclinical lipodystrophic mouse model of Bscl2 deficiency. We designed AAV vectors containing the mini/aP2 or thyroxine-binding globulin promoter to selectively target adipose or liver respectively. The AAV-aP2 vectors also contained the liver-specific microRNA-122 target sequence, restricting hepatic transgene expression. Systemic delivery of AAV-aP2 vectors overexpressing human BSCL2 restored adipose tissue development and metabolic health in lipodystrophic mice without detectable expression in the liver. High doses (1 × 1012 GCs) of liver-selective vectors led to off target expression and adipose tissue development, whilst low doses (1 × 1010 GCs) expressed selectively and robustly in the liver but did not improve metabolic health. This reveals that adipose tissue-selective, but not liver directed, AAV-mediated gene therapy is sufficient to substantially recover metabolic health in generalised lipodystrophy. This provides an exciting potential new avenue for an effective, targeted, and thereby safer therapeutic intervention.

2024-09-01·Journal of Diabetes Investigation

A multicenter, open‐label, single‐arm trial of the long‐term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE‐02)

Article

作者: Suzuki, Junichi ; Kakei, Yasumasa ; Wada, Jun ; Ogawa, Wataru ; Omori, Takashi ; Ebihara, Ken ; Urakami, Tatsuhiko ; Hirota, Yushi ; Katagiri, Hideki ; Imai, Junta

ABSTRACTAims/IntroductionInsulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01.Materials and MethodsThe primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02.ResultsTwenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis.ConclusionsEmpagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

2024-08-01·Diabetes, Obesity and Metabolism

Empagliflozin mitigates metabolic dysfunction‐associated steatotic liver disease by reducing de novo lipogenesis in a mouse model of lipoatrophic diabetes

Letter

作者: Deniel, Perrine ; Le May, Cédric ; Cariou, Bertrand ; Sotin, Thibaud ; Smati, Sarra ; Joubert, Michael ; Ducheix, Simon ; Arnaud, Lucie ; Hadjadj, Samy ; Prieur, Xavier

As a first preventive approach, we sought to assess whether empagliflozin could alter the development of hepatic steatosis in SKO mice.Eight-week-old SKO mice and their littermates wild-type (WT) mice were fed either an empagliflozin-supplemented diet (100 mg/kg) or a control diet for 8 wk.The liver mass was increased by four-fold in 16-wk-old SKO mice as compared with WT mice, and empagliflozin treatment reduced liver mass (35%), triglyceride (TG) content (50%) and Oil Red O staining (Figure 1A-C).Consistently, the mRNA levels of the lipid dropletassocd. protein Adrp, a marker of liver steatosis, were increased by three-fold in SKO mice compared with WT mice but were reduced by empagliflozin (Figure 1D).To understand further how empagliflozin limited liver steatosis development in SKO mice, we measured the mRNA levels of three main actors of de novo lipogenesis: Acly, Acc and Fas.MRNA levels of peroxisome proliferator-activated receptor alpha target genes involved in fatty acid utilization, such as Cpt1, Acot2 and Pdk4, were increased in SKO mice, empagliflozin had no addnl. effect (Figure 1J-L).Empagliflozin reduced glycemia (Figure S2C) without altering insulinemia or insulin sensitivity (Figure S2D,E). Empagliflozin treatment reduced liver mass by 19% and liver TG by 26% (Figure 2A-C).The empagliflozin significantly reduced mRNA levels of Adrp but not Mcp1 or Col1a1, suggesting a primary action on liver steatosis rather than on inflammation or fibrosis.Overall, these data showed that empagliflozin was able to improve established liver steatosis in older SKO mice and that this was still associated with a decrease in lipogenic gene expression.

项与脂肪萎缩性糖尿病相关的新闻（医药）

2024-06-14

·智慧芽新药科讯

IGF-1R 研究，触手可及：下载Word报告，紧跟科学前沿！

本报告由智慧芽新药情报库芽仔根据截止至2024年05月28日的新药情报数据库资料总结生成，如需下载包含截止至当前日期的最新数据Word格式报告，或希望获取其他任何靶点、适应症、药物类型、任意关键词专利的最新研究进展Word格式报告，请参阅文末提供的详细指南哦～ IGF-1R是胰岛素样生长因子1受体的简称，它在人体中起着重要的作用。IGF-1R通过调节细胞生长、增殖和凋亡等生物学过程，参与了细胞的分化和代谢调节。它还与肿瘤的发生和发展密切相关，因此成为了肿瘤治疗领域的研究热点。在制药行业的商务拓展中，IGF-1R的相关研究和药物开发具有重要的意义，可以为公司带来新的商机和发展机会。据智慧芽新药情报库统计，截止2024年05月28日，全球共有99个IGF-1R药物，来自127个机构，覆盖217个适应症，开展426个临床试验。研发进度靠前的Top 10药物如下：机构分析表1 根据靶点 IGF-1R 的药物研发阶段最高的机构分析表[表格1]，我们可以看到在该靶点下，Amgen, Inc.、ACADIA Pharmaceuticals, Inc.、Novartis AG、Takeda Pharmaceutical Co., Ltd.等公司的研发进展较为突出。首先，Amgen, Inc. 在该靶点下有2个药物已经获得批准上市，另外还有1个药物正在申请上市，显示出该公司在该领域的研发实力较为雄厚。而ACADIA Pharmaceuticals, Inc. 也有1个药物已经获得批准上市，另外还有1个药物正在申请上市，显示出该公司在该领域也有一定的研发成果。此外，Novartis AG 在该靶点下有1个药物已经获得批准上市，另外还有1个药物处于临床3期阶段，显示出该公司在该领域的研发进展也较为积极。Takeda Pharmaceutical Co., Ltd. 在该靶点下有1个药物已经获得批准上市，另外还有1个药物处于临床3期阶段，显示出该公司在该领域也有一定的研发实力。除了上述公司外，还有一些公司在该靶点下的研发进展也值得关注，比如Viridian Therapeutics, Inc. 在该靶点下有1个药物处于临床3期阶段，另外还有2个药物处于临床1期阶段，显示出该公司在该领域也有一定的研发潜力。另外，ImVax, Inc. 在该靶点下有1个药物处于临床2期阶段，另外还有1个药物处于临床前阶段，显示出该公司在该领域也有一定的研发实力。综上所述，针对靶点 IGF-1R，Amgen, Inc.、ACADIA Pharmaceuticals, Inc.、Novartis AG、Takeda Pharmaceutical Co., Ltd. 等公司在该领域的研发进展较为突出，其中Amgen, Inc. 的研发实力尤为突出，值得行业内其他公司进行学习和借鉴。适应症分析表2 根据提供的数据，我们可以看到在靶点 IGF-1R 下，已经有一些药物在相关适应症上被批准了，同时也有一些药物处于临床研发阶段或者非在研阶段。首先，让我们来看已经批准上市的适应症。根据 [表格2]，已经批准上市的适应症包括：ALK阳性非小细胞肺癌、Laron综合征、生长激素缺乏症、侏儒症、格雷夫斯眼病、Rett综合征、胰岛素样生长因子I缺乏症、非小细胞肺癌、生长障碍、胰岛素受体缺陷、脂肪萎缩性糖尿病、Donohue综合征、外周性原始神经外胚层肿瘤、尤文肉瘤、继发性肺恶性肿瘤、骨转移癌、胶质母细胞瘤、肝细胞癌、难治性尤文肉瘤、胰腺癌。这些适应症涵盖了多种疾病类型，包括肿瘤、遗传性疾病以及其他内分泌相关疾病。其次，对于非在研的适应症，我们可以看到在靶点 IGF-1R 下，有一些药物处于临床研发阶段或者非在研阶段。这些适应症包括格雷夫斯眼病、胰岛素样生长因子I缺乏症、外周性原始神经外胚层肿瘤、尤文肉瘤、胶质母细胞瘤、肝细胞癌、难治性尤文肉瘤、胰腺癌。这些疾病类型也涵盖了肿瘤和其他内分泌相关疾病。综上所述，靶点 IGF-1R 在药物研发中涉及的适应症非常广泛，包括肿瘤、遗传性疾病以及其他内分泌相关疾病。这表明该靶点在药物研发中具有重要的潜在应用价值，对于相关疾病的治疗具有一定的临床前景。因此，我们可以看到在当前靶点下已经有一些药物在相关适应症上被批准，同时也有一些药物处于临床研发阶段或者非在研阶段，这为未来的商务拓展提供了一定的市场机会和发展空间。药物类型分析表3 根据靶点 IGF-1R 的药物类型分析表[表格3]，我们可以看到在当前靶点下，小分子化药处于研发阶段的药物个数最多，分别为批准上市的2种、临床前的4种和非在研的27种。其次是单克隆抗体，分别为批准上市的1种、临床前的5种和非在研的21种。生长因子类药物也有一定数量的研发，其中批准上市的有3种、临床前的有1种、非在研的有4种。其他类型的药物研发数量相对较少。在这些生物仿制药的研发机构中，小分子化药的研发机构数量最多，反映了小分子化药在靶点 IGF-1R 上的研发进展较为活跃。同时，单克隆抗体的研发机构数量也较多，说明在这一领域也存在着一定的竞争压力。生长因子类药物的研发机构数量相对较少，但也不能忽视其在靶点 IGF-1R 上的研发潜力。综上所述，小分子化药和单克隆抗体是在靶点 IGF-1R 下研发进展最快的药物类型，其研发机构数量较多，竞争激烈。因此，在进行商务拓展时，需要重点关注这两类药物的研发情况，寻找合作机会和市场空间。同时，也要密切关注生长因子类药物的研发动态，把握其潜在的发展机会。近年交易概览表4 截止至2024年05月28日，根据表格4中提供的数据，我们可以看到在靶点 IGF-1R 下的药品交易情况。从2019年到2024年，交易次数呈现出不同的趋势。首先，2019年没有任何交易发生，这表明在该年份下，针对IGF-1R的药品交易并不活跃。其次，2020年和2021年的交易次数分别为2次和3次，虽然交易次数有所增加，但仍然可以被认为是相对不活跃的状态。然而，2022年的交易次数达到了4次，这表明在该年份下，针对IGF-1R的药品交易开始呈现出增长的趋势。 2023年的交易次数虽然减少至2次，但是交易总金额却大幅增加至27800.0百万美元，这表明尽管交易次数减少，但交易金额却大幅增加，显示出了交易的活跃度和金额的增长。最后，2024年的交易次数虽然只有1次，但是由于数据不完整，无法对该年份的交易趋势做出准确的判断。综上所述，根据表格4中的数据，我们可以看到在靶点 IGF-1R 下的药品交易在过去几年呈现出了不同的趋势，从不活跃到逐渐增长，再到交易次数减少但交易金额大幅增加。这些趋势表明，该行业的合作动态和潜在的财务调整正在发生变化，需要进一步关注和分析。国家/地区分析表5 根据提供的数据，我们可以看出在靶点 IGF-1R 下，美国、欧盟、日本等国家/地区在药物研发阶段的数量较多，其中美国在临床前和非在研阶段的药物数量最多，分别为11和50个。而中国在靶点 IGF-1R 下的药物研发也有一定进展，批准上市、临床前和非在研阶段的药物数量分别为2、2和7个。从数据中可以看出，中国在靶点 IGF-1R 的药物研发阶段数量虽然不及美国等国家，但也呈现出一定的发展势头。随着中国在医药领域的不断发展和政策的支持，预计中国在靶点 IGF-1R 下的药物研发将会有更多的进展。综上所述，当前在靶点 IGF-1R 下，美国、欧盟、日本等国家/地区的药物研发较为活跃，而中国也在逐渐加大在该领域的投入和研发力度，未来有望取得更多进展。报告获取详细指南 Step 1 复制下方链接至PC端浏览器打开，非注册登录用户请复制该页面打开后根据页面提示进行注册登录 https://synapse-zhihuiya-com.libproxy1.nus.edu.sg/target/13800a50d8f04c5c8cf73efc150d572e Step 2 点击页面中部右边悬浮芽仔按钮（本页面截图为展示Demo） Step 3 点击下载总结报告即可。意见反馈嗨，亲爱的朋友们！这份报告是由我们的新药情报库智慧小助手“芽仔”快速整理出来的哦。如果你在查看报告或者下载的时候遇到任何问题，或者有什么想对我们说的，别犹豫，直接扫一扫下面的二维码，找我们的小伙伴聊聊吧！而且，如果你的反馈对我们有帮助，我们还会送你一份小礼物——新药情报库的VIP账号，让你享受14到30天的免费使用权！快来和我们互动，一起让这份报告变得更棒吧！

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