Stonehouse Anthony, Okerson Ted, Kendall David, Maggs David
Amylin Pharmaceuticals, Inc., 9360 Towne Centre Dr., San Diego, CA 92121, USA.
Curr Diabetes Rev. 2008 May;4(2):101-9. doi: 10.2174/157339908784220705.
Type 2 diabetes is a chronic disease characterized by impaired insulin action, progressive beta cell dysfunction as well as abnormalities in pancreatic alpha cell function and postprandial substrate delivery. These pathophysiologic defects result in both persistent and progressive hyperglycemia, resulting in increased risk of both microvascular and cardiovascular complications. Traditional treatments for type 2 diabetes have focused on impaired insulin secretion and insulin resistance. These strategies are typically used in a stepwise manner: employing oral glucose lowering agents, followed by insulin therapy. This traditional approach fails to address the progressive decline in beta cell function. Moreover, these therapies are often associated with weight gain in overweight or obese patients with type 2 diabetes. Both exogenous insulin and insulin secretagogues are associated with an increased risk of hypoglycemia. Recently, new treatments that leverage the glucoregulatory effects of incretin hormones, such as glucagon like peptide 1 have been introduced. Both incretin mimetics and DPP-4 inhibitors address both the underlying pathophysiology and overcome several of the limitations of established therapies by providing improvements in glycemia, and control of body weight with minimal risk of hypoglycemia.
2型糖尿病是一种慢性疾病，其特征为胰岛素作用受损、β细胞功能进行性障碍以及胰腺α细胞功能和餐后底物输送异常。这些病理生理缺陷会导致持续性和进行性高血糖，从而增加微血管和心血管并发症的风险。2型糖尿病的传统治疗方法主要针对胰岛素分泌受损和胰岛素抵抗。这些策略通常按步骤使用：先使用口服降糖药，然后进行胰岛素治疗。这种传统方法无法解决β细胞功能的进行性下降问题。此外，这些疗法常常会导致2型糖尿病超重或肥胖患者体重增加。外源性胰岛素和胰岛素促分泌剂都与低血糖风险增加有关。最近，已经引入了利用肠促胰岛素激素（如胰高血糖素样肽1）的血糖调节作用的新疗法。肠促胰岛素类似物和二肽基肽酶-4（DPP-4）抑制剂既能解决潜在的病理生理学问题，又能通过改善血糖和控制体重、将低血糖风险降至最低来克服现有疗法的若干局限性。
