Edelman Steve, Maier Holly, Wilhelm Ken
Division of Diabetes/Metabolism, VA San Diego Healthcare Center, San Diego, California 92161, USA.
BioDrugs. 2008;22(6):375-86. doi: 10.2165/0063030-200822060-00004.
Pramlintide, the first member of a new class of drugs for the treatment of insulin-using patients with type 2 or type 1 diabetes mellitus, is an analog of the peptide hormone amylin. Amylin is co-secreted with insulin from pancreatic beta cells and acts centrally to slow gastric emptying, suppress postprandial glucagon secretion, and decrease food intake. These actions complement those of insulin to regulate blood glucose concentrations. Amylin is relatively deficient in patients with type 2 diabetes, depending on the severity of beta-cell secretory failure, and is essentially absent in patients with type 1 diabetes. Through mechanisms similar to those of amylin, pramlintide improves overall glycemic control, reduces postprandial glucose levels, and reduces bodyweight in patients with diabetes using mealtime insulin. Reductions in postprandial glucose and bodyweight are important, since postprandial hyperglycemia is associated with an increased risk of microvascular and macrovascular complications, and increased weight is an independent risk factor for cardiovascular disease. Pramlintide is generally well tolerated, with the most frequent treatment-emergent adverse event being mild to moderate nausea, which decreases over time. Pramlintide treatment is also associated with improvements in markers of oxidative stress and cardiovascular risk and improved patient-reported treatment satisfaction. These factors make pramlintide an attractive option for the treatment of postprandial hyperglycemia in patients with diabetes using mealtime insulin.
普兰林肽是用于治疗使用胰岛素的2型或1型糖尿病患者的新型药物类别中的首个成员,它是肽激素胰淀素的类似物。胰淀素与胰岛素从胰腺β细胞共同分泌,在中枢发挥作用,减缓胃排空、抑制餐后胰高血糖素分泌并减少食物摄入量。这些作用与胰岛素的作用相辅相成,以调节血糖浓度。根据β细胞分泌功能衰竭的严重程度,2型糖尿病患者体内的胰淀素相对缺乏,而1型糖尿病患者体内基本没有胰淀素。通过与胰淀素类似的机制,普兰林肽可改善整体血糖控制,降低餐后血糖水平,并使使用餐时胰岛素的糖尿病患者体重减轻。降低餐后血糖和体重很重要,因为餐后高血糖与微血管和大血管并发症风险增加相关,而体重增加是心血管疾病的独立危险因素。普兰林肽一般耐受性良好,最常见的治疗中出现的不良事件是轻度至中度恶心,且会随时间减轻。普兰林肽治疗还与氧化应激标志物和心血管风险的改善以及患者报告的治疗满意度提高相关。这些因素使普兰林肽成为治疗使用餐时胰岛素的糖尿病患者餐后高血糖的一个有吸引力的选择。