Exenatide Once Weekly, Cardiovascular Risk and Type-2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The glucagon-like peptide 1 (GLP-1) agonist exenatide represents an effective therapy in
      patients with type 2 diabetes mellitus (T2DM), which also seems to have some important
      non-glycemic effects. Yet, these non-glycemic effects are still largely unknown.

      The effect of exenatide once weekly was investigated in controlled, blinded and open-label
      clinical studies in subjects with T2DM who were controlled on diet and exercise alone or in
      combination with oral antidiabetic agents, but also in multi-dose controlled studies and such
      studies resulted in significant reductions in glycemic parameters (mean glycated hemoglobin
      (HbA1c), fasting serum/plasma glucose as well as postprandial plasma glucose levels), but
      also in body weight, over 24 to 30 weeks. Meaningful reductions were observed as early as
      week 4 of treatment, and maintained through 6 years of treatment.

      The study investigating cardiovascular effects of exenatide once weekly is currently
      undergoing. The results available are not numerous (such as DURATION-2, DURATION-3,
      DURATION-4 studies) and cannot lead to definitive conclusions.

      In this study the investigators will evaluate the effect of exenatide once-weekly on multiple
      cardiovascular risk markers. These markers are related to subclinical atherosclerosis,
      endothelial dysfunction, oxidative stress and atherogenic lipoproteins.

      The investigators will perform an open label, single-arm, prospective, intervention study
      using exenatide once weekly for a period of 8 months on 60 patients with T2DM.
    

Detailed description: 
      The research hypothesis is to assess whether exenatide once weekly can reduce subclinical
      atherosclerosis (as measured by carotid-intima media thickness [cIMT]) in patients with T2DM.

      The primary objective is to assess whether exenatide once weekly can reduce subclinical
      atherosclerosis (as measured by cIMT) in patients with T2DM.

      Primary endpoint: Reduction in cIMT. The secondary objective is to assess whether exenatide
      once weekly can reduce atherogenic lipoproteins, oxidative stress and endothelial dysfunction
      in patients with T2DM.

      Secondary endpoint: Reduction in atherogenic lipoproteins, oxidative stress and improvement
      of endothelial dysfunction.

      The purpose of the present 8 months study is to elucidate largely unknown non-glycemic
      effects of exenatide as add-on to metformin, including effects on cIMT, oxidative stress
      parameters and atherogenic lipoproteins, in addition to its benefit on glycemic control,
      weight loss and other efficacy parameters, as well as the safety profile of exenatide.

      The data for clinical and biochemical analyses, including collection of efficacy variables,
      ECG, pulse and physical examination, will be collected at baseline and after 8 months of
      therapy (at 6 months of the treatment, only the routine laboratory analyses, including HbA1c,
      will be performed).

      Clinical diagnostic tools will include the measurement of:

        1. cIMT, that will be assessed by B-mode real-time ultrasound using a single sonographer
           (Medison SonoAce Pico, with a probe of 7.5-10.0 MHz) in a standardized manner with fixed
           angles of insonation;

        2. Endothelial dysfunction, that will be assessed by flow mediated dilation of brachial
           artery.

      Biochemical analyses will include the analysis of:

        1. Routine testing: blood testing, liver and kidney profile, plasma lipids, glucose
           metabolism parameters;

        2. Oxidative stress parameters (plasma glutathione, serum lipid hydroperoxides, reactive
           oxygen species);

        3. Atherogenic lipoproteins, e.g. the analysis of 11 distinct lipoproteins including
           very-low-density lipoprotein (VLDL), 3 intermediate density lipoprotein (IDL) subclasses
           and 7 low density lipoprotein (LDL) subclasses.
    

Intervention name(s): Exenatide once weekly (BYDUREON™)
Intervention type(s): Drug
Intervention description(s): Exenatide is considered investigational medicinal product (IMP) and will be prescribed to enrolled patients in accordance with local requirements.
Exenatide will be available at a fixed dose of 2 mg and supplied as a kit. Exenatide should be injected subcutaneously (SC) in the thigh, upper arm (deltoid region) or abdomen. The injection site does not have to be consistent throughout the study. Injection can be done at any time of the day irrespective of meals. It is recommended that the time of injection is consistent throughout the study. Subjects will be instructed to perform an air shot before the first injection.
Subjects will follow a fixed dose of 2 mg
Other intervention name(s): BYDUREON™
Intervention MeSH terms: Exenatide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Exenatide once weekly; T2DM; IMT; Atherogenic lipoproteins