Drucker Daniel J, Nauck Michael A
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Lancet. 2006 Nov 11;368(9548):1696-705. doi: 10.1016/S0140-6736(06)69705-5.
Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.
胰高血糖素样肽1（GLP-1）是一种由肠道产生的肠促胰岛素激素，它能刺激胰岛素分泌、抑制胰高血糖素分泌、抑制胃排空，并减少食欲和食物摄入量。增强肠促胰岛素作用的治疗方法包括抗降解的GLP-1受体激动剂（肠促胰岛素类似物）和二肽基肽酶-4（DPP-4）活性抑制剂（肠促胰岛素增强剂）。使用肠促胰岛素类似物艾塞那肽（每日注射两次或长效释放剂型每周注射一次）和利拉鲁肽（每日注射一次）的临床试验表明，空腹和餐后血糖浓度以及糖化血红蛋白（HbA1c）水平降低（1%-2%），同时伴有体重减轻（2-5千克）。与GLP-1受体激动剂相关的最常见不良事件是轻度恶心，随着时间推移会减轻。口服DPP-4抑制剂，如西他列汀和维格列汀，可使HbA1c降低0.5%-1.0%，不良事件较少且不会导致体重增加。在临床前研究中，这些新型抗糖尿病药物以及肠促胰岛素类似物和增强剂还能增加β细胞量。然而，需要进行长期临床研究以确定靶向肠促胰岛素轴治疗2型糖尿病的益处。
