人胰高血糖素样肽-1类似物：利拉鲁肽

Human glucagon-like peptide-1 analogue-Liraglutide

胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素，具有促进胰岛素释放、延缓胃排空、减低体重和降低食欲等生理作用。然而，天然的GLP-1很不稳定，可被二肽基肽酶-Ⅳ（DPP-Ⅳ）降解，半衰期仅为1～2min。若采用天然GLP-1来降低血糖，需持续静脉输注或持续皮下注射，临床可行性较差。面对这种情况，人们不断探索，研发具有长效作用的人GLP-1类似物。本文着重论述此类药物的代表药物利拉鲁肽（liraglutide）。它的分子结构独特，通过和白蛋白结合，既保留了天然GLP-1的功效又延长了作用时间，可每日一次注射。临床应用中，它能安全、有效的控制糖代谢，改善胰岛β细胞功能，降低体重和收缩压。正是这种治疗的多效性，给2型糖尿病患者的治疗带来了新希望。

The incretin hormone glucagon-like peptide-1 （GLP-1） is a gut peptide with physiological functions such as insulin-releasing, gastric empty-delaying, body weight-lowering and appetite-reducing. However,due to the shortened half-life caused by enzymatic deactivation from dipeptidyl peptidase-Ⅳ （DPP-Ⅳ ） ,native GLP-1 has to be administered continuously through intravenous or injection to maintain its effectiveness. The complicated prerequisite hinders native GLP-1 to become a feasible glucose-lowering agent. Liraglutide is a once daily GLP-1 mimetic currently under development. While preserves the physiological trait of native GLP-1, liraglutide could sustain its clinical effect by binding to albumin thus prolong its metabolic time through its modified molecular structure. With its proved efficiency and safety in clinical studies and its various therapeutic effect such as glucose metabolism regulation, β-cell function restoration, body weight loss and systolic pressure reduction, liraglutide is expected to bring a new hope to patients with type 2 diabetes mellitus.