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，需要在这些患者中使用胰岛素。然而，尽管有智能胰岛素输送装置和连续葡萄糖监测，但大多数此类患者的血糖控制不佳。因此，我们研究了利拉鲁肽（一种GLP-1类似物）与胰岛素联合给药（胰岛素连续皮下输注（CSII））在此类患者中的作用。对这些患者进行连续血糖浓度（CGM）监测。胰岛素和利拉鲁肽联合给药导致空腹和平均血糖浓度在2 - 3天内降低，同时胰岛素剂量降低40%。高血糖和低血糖波动均显著减少。9周内体重、BMI、HbA 1c和CRP浓度下降。这种情况持续了24周。我们现在提出了第一项安慰剂对照前瞻性随机研究，以比较利拉鲁肽在1型糖尿病患者中与胰岛素治疗56周的有益作用。本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了利拉鲁肽在这些患者中的有益作用，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.