- 期刊
增泌素(Incretin)類藥物治療第2型糖尿病之臨床實證
Clinical Evidence of GLP-1 Receptor Agonists and DPP Ⅵ Inhibitors in the Treatment of Type 2 Diabetes
摘要
Incretin荷爾蒙（稱增泌素）降血糖的作用約二十年前就已經被發現，但增泌素荷爾蒙在糖尿病之治療近年來才非常受重視。除了刺激胰島素分泌的作用外，增泌素還有促進β細胞生長及分化的作用、以及減少β細胞凋零死亡。由於增泌素具葡萄糖依賴性的促胰島素分泌作用，所以藥理學上不會有低血糖的副作用。具增泌素效果之荷爾蒙中以類昇糖素肽胜－1（glucagon-like peptide-1，簡稱GLP-1）研究最多，最具治療學發展潛力。GLP-1之生理功能不只對胰島的作用，它還具作用在神經糸統、消化糸統、與循環糸統等胰島外的作用。GLP-1本身不能直接適用於臨床治療，主要原因是它很快就會被雙肽基肽胜酶Ⅳ（dipeptidyl peptidase Ⅳ，簡稱DPPIV）分解。最近發展出來的GLP-1作用藥物有兩大類：一類是藉由分子結構修飾後可抵抗DPP Ⅳ分解的GLP-1擬似物，如exenatide和liraglutide；另一類是藉由DPP Ⅳ抑制劑而延長患者體內自身GLP-1的血清半衰期而延長作用。最近臨床上應用於糖尿病治療的實證，這兩大類藥物均陸續有製劑獲得美國FDA核可用於第2型糖尿病的治療。增泌素類藥物之開發，對於第2型糖尿病治療學而言是一突破性之發展。增泌素類藥物治療對第2型糖尿病的心血管病風險與死亡風險的影響，則仍待長期臨床試驗實證。
並列摘要
Incretin plays an import role in postprandial insulin secretion. Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide have well been known to have properties of incretin effect. Patients with type 2 diabetes are noted to be with lost or severely impaired incretin effect. Therefore, the patients also have decresed postprandial insulin secretion. The major cause of impaired incretin effect in patients with type 2 diabetes is decrease in GLP-1 secretion. GLP-1 also has some effects on promotion of β cell growth and differentiation, decreasing β cell apoptosis, and glucagon suppression effect. In addition, some beneficial extrapancreatic effects, such as decreasing food intake by acting on central nervous system and direct action on cardiovascular system are also noted. Due to its glucose-dependent insulin secretion effect, the risk of hypoglycemia is low. The incretins are rapidly inactivated by dipeptidyl peptidase Ⅳ (DPP Ⅵ). Recently, two different approaches are developed to retard DPP Ⅵ action. One is to use GLP-1 receptor agonists that are resistant to degradation by DPP Ⅵ. These GLP-1 mimetics include exenatide and liraglutide. Another approach is to inhibit the activity of DPP Ⅵ so that half-life of endogenously released GLP-1 can be prolonged. These DPP Ⅵ inhibitors include sitagliptin and vildagliptin. The beneficial effects of these preparations on clinical parameters in patients with type 2 diabetes mellitus have recently been reported in some evidence-based studies.