Diabetes Mellitus (DM) is a complex and progressive disease in both adult and children that has a major societal and economic impact. The goal of new pathophysiological thinking in treatment of DM is to bring high blood glucose levels into control. Beside the lifestyle and metformin are the first line of treatment for type 2 DM, the rise of new anti-diabetes treatment developed as monotherapy or with traditional combination not only help to normalize glucose level and HbA1c but also target different aspects of DM related issues life weight, cardiovascular, kidney complication, etc.Pramlintide, preventative of amylin analogue, is used for treating type 1 and type 2 DM. GLP-1 and DPP4 inhibitors both act on incretin-related problems. Megligtinides increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. SGLT-2 inhibitors increase the excretion of glucose in the urine which is very unique feature. However, safety issues and efficacies of these new medications need further investigation to maximize the benefit of DM treatment.