LIRAGLUTIDE AS ADDITIONAL TREATMENT IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

利拉鲁肽作为 1 型糖尿病患者的额外治疗

• 批准号: 8297373
• 负责人: Paresh Dandona
• 金额: $ 27.48万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8297373
• 关键词: Acetaminophen; Affect; Aftercare; Agonist; American; Beta Cell; Blood Glucose; Body Weight; C-Peptide; Cell physiology; Cell secretion; Child; Dependence; Devices; Diabetic Angiopathies; Disease; Dose; Fasting; Fructosamine; Gastric Emptying; Gastroparesis; Glucagon; Glucose; Glycosylated hemoglobin A; Hour; Hyperglycemia; Hypoglycemia; Infusion procedures; Insulin; Insulin-Dependent Diabetes Mellitus; Investigation; Measures; Monitor; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Patients; Pharmaceutical Preparations; Physiological; Placebo Control; Placebos; Randomized; Recruitment Activity; Relative (related person); Research Design; Residual state; Sample Size; Testing; absorption; analog; base; blood glucose regulation; falls; fasting glucose; glucagon-like peptide; glucagon-like peptide 1; glucose monitor; glycemic control; improved; insulin secretion; liraglutide; prospective; subcutaneous; type I diabetic

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. PUBLIC HEALTH RELEVANCE: In view of the total dependence and the relative inadequacy of therapy based on insulin alone in patients with type 1 diabetes, we have investigated the effect of liraglutide as an addition to insulin in these patients. The dramatic and rapid improvement in glycemic control, glycemic excursions, HbA1c, body weight and CRP concentrations has led us to propose this prospective, randomized study on the effect of liraglutide in type 1 diabetics. If confirmed, liraglutide and other GLP-1 agonists may become routine in the treatment of this condition.

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。 公共卫生关系：考虑到1型糖尿病患者中基于胰岛素单药治疗的完全依赖性和相对不足，我们研究了利拉鲁肽作为胰岛素辅助治疗在这些患者中的作用。血糖控制、血糖波动、HbA 1c、体重和CRP浓度的显着而快速的改善促使我们提出了这项关于利拉鲁肽对1型糖尿病患者影响的前瞻性随机研究。如果得到证实，利拉鲁肽和其他GLP-1激动剂可能成为治疗这种疾病的常规药物。