The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes. A 26 Week, Randomised, Open-label, Parallel-group, Multicentre, Multinational Trial With a 26 Week Extension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 987
- 试验地点
- 1
- 主要终点
- Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26.
研究概览
简要总结
This trial is conducted in Europe and North America. The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will continue their own pre-trial metformin treatment during the trial.
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
- None
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects diagnosed with type 2 diabetes, insulin naïve and treated with metformin as monotherapy for at least 3 months prior to screening, at a stable dose of at least 1500 mg/day or metformin (at least 1500 mg/day) and a sulfonylurea (less than or equal to half of the maximum approved dose), both at a stable dose for at least 3 months prior to screening. Previous short-term insulin treatment in connection with intercurrent illness is allowed at the discretion of the Investigator
- •HbA1c 7.0-10.0% (both inclusive) for subjects on metformin monotherapy
- •HbA1c 7.0-8.5% (both inclusive) for subjects on metformin in combination with a sulphonylurea
排除标准
- •Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness at the discretion of the Investigator)
- •Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 3 months prior to screening
- •Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator
- •Impaired kidney function
- •Impaired liver function
- •Uncontrolled treated/untreated hypertension
- •Cancer or any clinically significant disease or disorder as judged by the Investigator
- •Previous participation in the run-in phase of this trial. Re-screening is allowed once
- •History of chronic pancreatitis or idiopathic pancreatitis
研究组 & 干预措施
Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
干预措施: liraglutide (Drug)
Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
干预措施: metformin (Drug)
Insulin detemir + Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
干预措施: liraglutide (Drug)
Insulin detemir + Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
干预措施: insulin detemir (Drug)
Insulin detemir + Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
干预措施: metformin (Drug)
Non-Randomised Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%
干预措施: liraglutide (Drug)
Non-Randomised Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%
干预措施: metformin (Drug)
Early Withdrawals Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial
干预措施: liraglutide (Drug)
Early Withdrawals Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial
干预措施: metformin (Drug)
Intensified group
Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
干预措施: liraglutide (Drug)
Intensified group
Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
干预措施: insulin detemir (Drug)
Intensified group
Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
干预措施: metformin (Drug)
结局指标
主要结局
Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26.
时间窗: Week 0 (Randomisation), week 26
次要结局
- Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF)(Week 0, Week 52)
- Mean Change From Randomisation in Fasting Plasma Glucose at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Fasting Insulin at Week 52(Week 0 (Randomisation), Week 52)
- Mean Change From Randomisation in Waist Circumference at Week 26.(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Fasting Pro-insulin at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in Fasting C-peptide at Week 26.(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group)(Week 0, Week 52)
- Mean Change From Randomisation in Fasting Plasma Glucose at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in Fasting Insulin at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Fasting Pro-insulin at Week 26.(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Fasting C-peptide at Week 52.(Week 0, Week 52)
- Mean Changes From Randomisation in Cholesterol Lipids at Week 52.(Week 0, Week 52)
- Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in Body Weight at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in Hip Circumference at Week 52(Week 0, week 52)
- Mean Changes From Randomisation in Cholesterol Lipids at Week 26.(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Lipids: Triglycerides at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Lipids: Triglycerides at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in Waist Circumference at Week 52.(Week 0, Week 52)
- Mean Change From Randomisation in Hip Circumference at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 52.(Week 0, Week 52)
- Adverse Events From Run-in (Week -12) to Week 52(Run-in (week -12) to Week 52)
- Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26(weeks 0-26)
- Mean Change From Randomisation in Waist to Hip Ratio at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Waist to Hip Ratio at Week 52(Week 0, Week 52)
- Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 26.(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 26(Week 0 (Randomisation), Week 26)
- Mean Change From Randomisation in Body Weight at Week 26(Week 0 (Randomisation), Week 26)
- Hypoglycaemic Episodes Weeks 0-52(Week 0-52)