Impact of Liraglutide on Endothelial Function and Microvascular Blood Flow in Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The trial is a phase IV clinical trial investigating the impact of Liraglutide on endothelial
      function and microvascular blood flow in 44 patients with type 2 diabetes mellitus aged 30-65
      and HbA1c ranging from ≥ 5.5% ≤ 7.0%. The patients will be randomized into two study arms,
      one arm will be treated with Metformin monotherapy, the second arm will be treated with
      Metformin and Liraglutide at an increasing dose (0.6 mg/day to 1.8 mg/day.)
    

Detailed description: 
      Type 2 Diabetes Mellitus (DM) is associated with increased cardiovascular risk and the
      majority of type 2 diabetic patients die due to the vascular complications of Diabetes
      Mellitus. In type 2 diabetic patients, an early marker in the biogenesis of atherosclerosis
      and cardiovascular disease is the occurrence of endothelial dysfunction with subsequent
      deterioration in micro- and macrovascular blood flow and tissue supply. Also several
      mechanistic pathways linking Diabetes Mellitus with endothelial dysfunction and
      cardiovascular complications are postulated. Recent studies aimed to investigate the
      vasoprotective effect of strict glycaemic control using conventional treatment algorithms
      failed to reduce cardiovascular risk in patients with Diabetes Mellitus type 2. Numerous
      pharmacological drugs are available to reduce blood glucose levels in type 2 diabetic
      patients. Beside comparable glucose lowering efficacy, some of them evolve limited or even
      adverse effects on vascular function and cardiovascular risk. Therefore, ideally new
      treatments in Diabetes Mellitus type 2 provide more than just reducing blood glucose values.
      Future treatments in type 2 Diabetes Mellitus will be judged on their potency to affect the
      cardiovascular risk profile in patients with Diabetes Mellitus type 2.

      Liraglutide is a Glucagon-like peptide-1 (GLP-1) analogue shown to be effective in the
      treatment of type 2 Diabetes Mellitus. Liraglutide was shown to improve blood glucose levels
      not only by stimulating insulin secretion from the β cell, but also by improving the
      conversion of intact proinsulin into insulin and C-peptide in the granula of the β cell.
      While in rodents, GLP-1 and its analogues showed an increase in β cell regeneration and an
      inhibitory effect on β cell apoptosis, the effect of GLP-1 analogues on β cell mass in humans
      is less clear. Beyond its effects on β cells, Liraglutide and other GLP1 analogues were shown
      to suppress the glucagon release from α cells and to evolve a supportive effect on weight
      reduction by central and probably peripheral effects.

      Beside these effects of GLP-1-analogues on β cell physiology and glucose metabolism, recent
      studies suggested several pleiotrophic effects of GLP-1 treatment which go beyond glycaemic
      control. Receptors for GLP-1 have been located in myocardial and endothelial cells, and GLP-1
      supplementation was found to improve myocardial and endothelial function in diabetic and in
      non-diabetic subjects. In endothelial cells, isolated from human coronary arteries, GLP-1
      rapidly activates endothelial nitric oxide synthase (eNOS) and stimulates nitric oxide (NO)
      production, promotes cell proliferation and inhibits glucolipoapoptosis. In addition, in
      transformed vascular endothelial cells, GLP-1 protects endothelial dysfunction incurred by
      tumor necrosis factor-α (TNF-α) through the modulation of the expression of vascular adhesion
      molecules and plasminogen activator inhibitor-1 (PAI-1). Chronic administration of GLP-1
      analogues is associated with a significant reduction in blood pressure. Therefore it seems
      conceivable, that in patients with Diabetes Mellitus type 2, treatment with the GLP-1 analog
      Liraglutide might improve the cardiovascular risk profile beyond glucose control by
      stimulating endothelial NO release and by improving endothelial function.

      The goal of our study is to investigate the vascular and endothelial effects of adding
      Liraglutide treatment to type 2 diabetic patients previously treated with Metformin.
    

Intervention name(s): Victoza®
Intervention type(s): Drug
Intervention description(s): Patients taking Metformin at individual dose and Liraglutide 0.6 mg once daily for the 1st week, 1.2 mg daily for another 5 weeks, 1.8 mg daily for another 6 weeks. When arrived at the dosage of 1.8 mg daily and the dose is not tolerated by the patient, the dose of Liraglutide can be decreased.Liraglutide is injected in the subcutaneous tissue once daily
Other intervention name(s): Victoza®, Liraglutide
Intervention MeSH terms: Liraglutide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes Mellitus treatment Metformin