LIRAGLUTIDE AS ADDITIONAL TREATMENT IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

描述（由申请人提供）：1型糖尿病患者β细胞功能丧失需要使用胰岛素。然而，尽管有智能的胰岛素输送装置和持续的血糖监测，大多数这样的患者并没有得到很好的控制。因此，我们研究了利拉鲁肽（GLP-1类似物）与胰岛素联合作为持续皮下输注胰岛素（CSII）在此类患者中的作用。连续监测这些患者的葡萄糖浓度（CGM）。胰岛素和利拉鲁肽联合使用可在2 - 3天内降低空腹血糖和平均血糖浓度，同时胰岛素剂量减少40%。高血糖和低血糖的短途旅行都有明显的减少。9周内体重、BMI、HbA1c和CRP浓度均有所下降。这种情况持续了24周。我们现在提出了第一个安慰剂对照前瞻性随机研究，比较利拉鲁肽对1型糖尿病患者56周胰岛素治疗的有益效果。这项研究还将评估利拉鲁肽是否在餐后发挥胰高血糖素抑制作用。如果这项研究确实证实利拉鲁肽对这些患者有益，它可能成为1型糖尿病治疗的常规部分，显著改善葡萄糖稳态，因此可能减少糖尿病的微血管并发症。

DESCRIPTION (provided by applicant): The loss of beta-cell function in type 1 diabetes necessitates the use of insulin in these patients. However, a majority of such patients are not well controlled in spite of clever insulin delivering devices and continuous glucose monitoring. We, therefore, investigated the effect of liraglutide, a GLP-1 analog in combination with insulin given as a continuous subcutaneous infusion of insulin (CSII) in such patients. These patients were monitored continuously for glucose concentrations (CGM). The combination of insulin and liraglutide resulted in the reduction of fasting and mean blood glucose concentrations within 2 to 3 days with a concomitant reduction in the dose of insulin by 40%. There was a marked reduction in both hyperglycemic and hypoglycemic excursions. There was a fall in body weight, BMI, HbA1c and CRP concentrations within 9 weeks. This persisted over a period of 24 weeks. We now propose the first placebo controlled prospective, randomized study to compare the beneficial effect of liraglutide in type 1 diabetics on treatment with insulin for 56 weeks. This study will also assess whether liraglutide exerts a glucagon suppressive action post- prandially. If indeed, this study confirms a beneficial effect of liraglutide in these patients, it could becom a routine part of the treatment of type 1diabetes with marked improvements in glucose homeostasis and, therefore, a potential reduction in microvascular complications of diabetes.