Liraglutide in Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- HbA1c (%)
研究概览
简要总结
The glucose lowering effects of GLP-1 agonists are well established in subjects with type 2 diabetes, however, these have not been studied prospectively in subjects with type 1 diabetes. The investigators have, therefore, designed this study to investigate the central hypothesis that in patients with type 1 diabetes, Liraglutide has a glucose lowering effect. A major secondary objective of this study is to elucidate the mechanisms responsible for its glucose lowering effects and those involved in reducing the insulin dose. The specific aims of this proposal are:
Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases HbA1c, fasting, postprandial and the overall mean glucose concentrations while decreasing the dose of insulin required.
Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases basal and postprandial glucagon concentrations and increases basal and postprandial C-peptide concentrations.
Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric emptying.
详细描述
The control of glucose homeostasis in subjects with type 1 diabetes is fragile since exogenous insulin cannot compensate for changing requirements and is not precise either in terms of the dose or the bio-availability of the insulin injected. Furthermore, in the near total absence of insulin secretion, the physiological post prandial inhibition of glucagon secretion by the α-cell is also probably deficient in all type 1 diabetics. Thus, there is a need for therapies beyond insulin that can further improve glycemic control and reduce fluctuations in glucose in these subjects. The investigators have recently shown that Liraglutide, a glucagon like peptide (GLP)-1 analogue with duration of action of 24 hours, when added to insulin in subjects with well controlled type 1 diabetes reduces mean and standard deviation of blood glucose, HbA1c and insulin requirements. Since C-peptide concentrations did not alter following Liraglutide, it is likely that the suppression of glucagon may have contributed to this effect. The glucose lowering effects of GLP-1 agonists are well established in subjects with type 2 diabetes, however, these have not been studied prospectively in subjects with type 1 diabetes. The investigators have, therefore, designed this study to investigate the central hypothesis that in patients with type 1 diabetes, Liraglutide has a glucose lowering effect. A major secondary objective of this study is to elucidate the mechanisms responsible for its glucose lowering effects and those involved in reducing the insulin dose. The specific aims of this proposal are:
Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases HbA1c, fasting, postprandial and the overall mean glucose concentrations while decreasing the dose of insulin required.
Aim 1.1: To compare the HbA1c, mean fasting, glucose, mean weekly glucose, standard deviation of weekly blood glucose concentrations as recorded by continuous glucose monitoring and the dose of insulin required prior to and following 52 weeks of treatment with 1.8 mg of liraglutide daily.
Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and after 52 weeks of treatment with 1.8 mg of liraglutide daily.
Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases basal and postprandial glucagon concentrations and increases basal and postprandial C-peptide concentrations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII; also known as insulin pump) or multiple (four or more) injections of insulin per day.
- •Regularly measuring blood sugars four times daily.
- •HbA1c of less than 8.5%.
- •Well versed with carbohydrate counting.
- •Age 18-75 years.
- •BMI 20-40 kg/m2
排除标准
- •Type 1 diabetes for less than 6 months;
- •Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks;
- •Hepatic disease (transaminase > 3 times normal) or cirrhosis;
- •Renal impairment (serum eGFR < 30ml/min/1.73m2);
- •HIV or Hepatitis B or C positive status;
- •Participation in any other concurrent clinical trial;
- •Any other life-threatening, non-cardiac disease;
- •Use of an investigational agent or therapeutic regimen within 30 days of study.
- •history of pancreatitis
- •inability to give informed consent
- •history of gastroparesis
- •history of medullary thyroid carcinoma or MEN 2 syndrome.
研究组 & 干预措施
Liraglutide 1.8mg
Daily Injection
干预措施: Liraglutide 1.8mg (Drug)
Placebo
Daily Injection
干预措施: Placebo (Drug)
结局指标
主要结局
HbA1c (%)
时间窗: 52 Weeks
HbA1c measured at baseline and after 52 weeks of treatment with Liraglutide or placebo.
次要结局
- Mean Weekly Glucose Concentrations.(52 Weeks)
- Body Weight(52 weeks)
研究者
Paresh Dandona
Director, Diabetes-Endocrinology Center of Western NY
University at Buffalo