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潜在未来抗糖尿病药物的叙述性综述:我们还能期待更多吗?

A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

作者信息

Chikara Gaurav, Sharma Pramod Kumar, Dwivedi Pradeep, Charan Jaykaran, Ambwani Sneha, Singh Surjit

机构信息

Dr. Sampurnanand Medical College-Jodhpur, Residency Road, Sector-D, Shastri Nagar, Jodhpur, 342003 Rajasthan India.

2All India Institute of Medical Sciences (AIIMS)-Jodhpur, Basni Industrial Area Phase-2, Jodhpur, Rajasthan 342005 India.

出版信息

Indian J Clin Biochem. 2018 Apr;33(2):121-131. doi: 10.1007/s12291-017-0668-z. Epub 2017 Jun 8.

DOI:10.1007/s12291-017-0668-z
PMID:29651202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5891460/
Abstract

Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.

摘要

糖尿病是一种以高血糖为特征的慢性代谢疾病,其在全球范围内的患病率正在上升。大多数病例属于2型糖尿病(T2DM)。在全球范围内,印度成年人的糖尿病患病率位居第二。目前可用的治疗药物类别单独使用或联合使用,但很少能达到治疗目标。T2DM领域多样的病理生理学以及对具有更有利药代动力学-药效学特征的治疗药物的需求使得新型药物的发现至关重要。大量分子,其中一些具有新机制,正处于研发阶段。本综述的要点是根据其研发阶段,特别是那些处于3期或2期的药物,追踪和讨论这些潜在药物。正在为现有药物类别如胰岛素、DPP-4抑制剂、GLP-1类似物;以及新的药物类别如双/泛PPAR激动剂、双SGLT1/SGLT2抑制剂、格列明、抗炎药、葡萄糖激酶激活剂、G蛋白偶联受体激动剂、杂合肽激动剂、顶端钠依赖性胆汁酸转运体(ASBT)抑制剂、胰高血糖素受体拮抗剂等开发独特的分子。表型相似患者中异质性的临床表现和治疗结果提示我们应超越标准治疗策略进行思考。

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A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?潜在未来抗糖尿病药物的叙述性综述:我们还能期待更多吗?
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本文引用的文献

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Omarigliptin for the treatment of type 2 diabetes mellitus.奥格列汀用于治疗2型糖尿病。
Expert Opin Pharmacother. 2016 Oct;17(14):1947-52. doi: 10.1080/14656566.2016.1218472.
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Glucose and lipid effects of the ileal apical sodium-dependent bile acid transporter inhibitor GSK2330672: double-blind randomized trials with type 2 diabetes subjects taking metformin.回肠顶端钠依赖性胆汁酸转运体抑制剂GSK2330672对葡萄糖和脂质的影响:对服用二甲双胍的2型糖尿病受试者进行的双盲随机试验
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G protein-coupled receptors as targets for anti-diabetic therapeutics.G 蛋白偶联受体作为抗糖尿病治疗的靶点。
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Imeglimin: A Potential New Multi-Target Drug for Type 2 Diabetes.依美格列明:一种用于2型糖尿病的潜在新型多靶点药物。
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Trelagliptin: First Global Approval.特利格列汀:全球首次获批。
Drugs. 2015 Jul;75(10):1161-4. doi: 10.1007/s40265-015-0431-9.
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Deciphering metabolic messages from the gut drives therapeutic innovation: the 2014 Banting Lecture.解读来自肠道的代谢信息推动治疗创新:2014年班廷讲座
Diabetes. 2015 Feb;64(2):317-26. doi: 10.2337/db14-1514.
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Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: a randomised, double-blind, phase 3, non-inferiority study.每周一次替格列汀对比每日一次阿格列汀治疗日本 2 型糖尿病患者的随机、双盲、III 期、非劣效性研究。
Lancet Diabetes Endocrinol. 2015 Mar;3(3):191-7. doi: 10.1016/S2213-8587(14)70251-7. Epub 2015 Jan 19.
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GPR40 agonists for the treatment of type 2 diabetes: life after 'TAKing' a hit.GPR40 激动剂治疗 2 型糖尿病:“TAKing”一击后的生活。
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Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.洛格列酮和吡格列酮作为二甲双胍的附加治疗用于2型糖尿病患者:一项为期24周的多中心、随机、双盲、平行组、活性药物对照的III期临床试验,并延长28周。
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Addressing unmet medical needs in type 2 diabetes: a narrative review of drugs under development.解决2型糖尿病未满足的医疗需求:对正在研发的药物的叙述性综述
Curr Diabetes Rev. 2015;11(1):17-31. doi: 10.2174/1573399810666141224121927.