维格列汀的研发及糖尿病治疗中的应用

Research and development of Vildagliptin and its application in the treatment of diabetes mellitus

DM的发病机制从最初的"三英会"发展到目前的"八重奏",而降糖药物也从传统降糖药发展到新型降糖药。肠促胰素有葡萄糖依赖性促胰岛素分泌多肽(GIP)和胰升糖素样肽1(GLP-1)两种,但GLP-1体内存活时间很短,迅速被二肽基肽酶4(DPP-4)分解。1998年,Edwin Villhauer博士率先发明和确定了可用于临床试验的DPP-4抑制剂LAF-237(维格列汀),DPP-4抑制剂可使DPP-4失活,从而不分解GLP-1,通过提高GLP-1的水平,发挥控制BG的作用。维格列汀是国内适应症最广泛的DPP-4抑制剂之一,可单药、联合二甲双胍、联合磺脲、联合Ins使用,用于DM患者全程治疗。维格列汀属于底物性抑制剂,通过共价键与DPP-4酶结合,稀释后仍能在很大程度上抑制DPP-4酶活性,耐受性良好,长期安全性高,可用于NYHA心功能分级Ⅰ~Ⅲ级患者。

The pathogenesis of diabetes has developed from the original"three Ying Hui"to the current"octet",and hypoglycemic drugs have also developed from traditional hypoglycemic drugs to new hypoglycemic drugs.There are two kinds of glucagon like peptide(GLP-1)and glucose dependent insulin like peptide(GIP).However,GLP-1 has a short survival time in vivo and is rapidly decomposed by dipeptidyl peptidase 4(DPP-4).In 1998,Dr.Edwin villhauer first invented and identified the DPP-4 inhibitor laf-237(Vildagliptin)which can be used in clinical trials.DPP-4 inhibitors can inactivate DPP-4,so as not to decompose GLP-1.By increasing the level of GLP-1,Dr.Edwin Villhauer first invented and determined the DPP-4 inhibitor laf-237(Vildagliptin),which can be used in clinical trials.Vildagliptin is one of the most widely used DPP-4 inhibitors in China.It can be used as a single drug,combined with Metformin,combined with sulfonylurea and insulin,and can be used in the whole treatment of diabetic patients.Vildagliptin is a kind of substrate inhibitor.It can bind with DPP-4 enzyme through covalent bond.It can still inhibit the activity of DPP-4 enzyme to a great extent after dilution.It has good tolerance and high long-term safety.It can be used in patients with NYHA cardiac function grade Ⅰ~Ⅲ.