Liraglutide in Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.

      Aim 2.1: To compare the basal and postprandial glucagon and C-peptide concentrations
      following a test meal before and after 52 weeks of treatment with 1.8 mg of liraglutide
      daily.

      Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric
      emptying.

      Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and
      after treatment with 1.8 mg of daily subcutaneous liraglutide.
    

Intervention name(s): Liraglutide 1.8mg; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Liraglutide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment