Chikara Gaurav, Sharma Pramod Kumar, Dwivedi Pradeep, Charan Jaykaran, Ambwani Sneha, Singh Surjit
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.
Indian J Clin Biochem. 2018 Apr;33(2):121-131. doi: 10.1007/s12291-017-0668-z. Epub 2017 Jun 8.
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.
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。