糖尿病是一種代謝障礙性疾病,患病率逐年上升,已成為全球慢性非傳染性疾病中最具流行性的疾病。糖尿病患者中以2型糖尿病患者為主,占比超過90%?，F(xiàn)有糖尿病治療藥物主要包括磺脲類、雙胍類、格列奈類、噻唑烷二酮類、α-葡萄糖苷酶抑制劑、胰高血糖素樣肽-1(GLP-1)受體激動(dòng)劑、二肽基肽酶IV(DPP-4)抑制劑和鈉-葡萄糖協(xié)同轉(zhuǎn)運(yùn)蛋白2(SGLT2)抑制劑。它們在降糖控糖作用機(jī)制上各具特點(diǎn)和優(yōu)勢,但仍不能滿足臨床治療的需求。隨著研究人員的不斷探索,一些治療2型糖尿病的新靶點(diǎn)化合物已進(jìn)入臨床I、II期研究,并有多個(gè)化合物處于臨床前研發(fā)中,有望成為2型糖尿病的治療藥物。介紹了葡萄糖激酶激動(dòng)劑、胰高血糖素受體拮抗劑、G蛋白偶聯(lián)受體119(GPR119)激動(dòng)劑、腺苷酸活化蛋白激酶(AMPK)激動(dòng)劑、游離脂肪酸受體1(FFAR1)激動(dòng)劑、蛋白酪氨酸磷酸酶-1B(PTP-1B)抑制劑和11β-羥類固醇脫氫酶1(11β-HSD1)抑制劑的作用機(jī)制、研發(fā)進(jìn)程和注意事項(xiàng),希望為2型糖尿病治療藥物的研發(fā)提供參考。

Diabetes is a kind of metabolic disorders. Its incidence is rising year by year, and has become one of the most popular non-communicable chronic diseases in the world. Above 90% of diabetic patients suffer type 2 diabetes. The current drugs for type 2 diabetes mainly include sulfonylureas, biguanides, glinides, thiazolidinediones, α-glucosidase inhibitor, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase IV (DPP-IV) inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors. Each has its characteristics and advantages on the hypoglycemic mechanism of controlling sugar, but can not meet the clinical demand. With the constant efforts of researchers, a lot of compounds with new targets for type 2 diabetes have been in phase I, or II clinical study, and a few are in pre-registration condition, which is expected to clinical application in treatment of type 2 diabetes mellitus as new drugs. In this paper, mechanisms of new targets, research process and notice of drugs for anti-type 2 diabetes, such as glucokinase agonists, glucagon receptor inhibitors, G-protein coupled receptor 119 (GPR119) agonists, AMP-activated protein kinase (AMPK) agonists, free fatty acid receptor 1(FFAR1) agonists, protein tyrosine phosphatase-1B (PTP-1B) inhibitors, and 11β-hydroxysteroid dehy drogenase (11β-HSD) inhibitors are reviewed, which could provide a reference for R & D of drugs for type 2 diabetes.