Hughes Thomas E
Zafgen, Inc., 5 Cambridge Center, Floor 2, Cambridge, MA 02142, United States.
Curr Opin Chem Biol. 2009 Jun;13(3):332-7. doi: 10.1016/j.cbpa.2009.04.622. Epub 2009 May 23.
Type 2 diabetes and obesity remain the focus of investigational drugs for metabolic disease. Only one new class of agents (Dipeptidylpeptidase 4 Inhibitors) has been approved in this field for control of blood glucose in patients with type 2 diabetes. Significant progress has been made in the elucidation of pathways of interest for new therapies in diabetes and obesity, partly through advances in human genetics that have highlighted genetic loci relevant to pancreatic beta cell dysfunction and hypothalamic control of food intake, respectively. Investigational drugs targeting these pathways are in early clinical investigation, including GPR119 agonists. Compounds targeting lipid partitioning and lipid biosynthetic enzymes also have emerged, including inhibitors of the enzymes DGAT1 and SCD1.
2型糖尿病和肥胖症仍是代谢疾病研究药物的重点。在该领域，仅有一类新型药物（二肽基肽酶4抑制剂）被批准用于控制2型糖尿病患者的血糖。在阐明糖尿病和肥胖症新疗法的相关途径方面已取得显著进展，部分原因是人类遗传学的进步分别突出了与胰腺β细胞功能障碍和下丘脑食物摄入控制相关的基因位点。针对这些途径的研究药物正处于早期临床研究阶段，包括GPR119激动剂。针对脂质分配和脂质生物合成酶的化合物也已出现，包括二酰甘油酰基转移酶1（DGAT1）和硬脂酰辅酶A去饱和酶1（SCD1）的抑制剂。
