Mineralocorticoid Receptor Antagonists in Type 2 Diabetes
Condition: Diabetes Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this study is to investigate the effect of selective blocking of the
      mineralocorticoid receptor in patients with type 2 diabetes on insulin resistance, lipid
      metabolism and myocardial function.
    

Detailed description: 
      In this randomized, double-blind, placebo-controlled study we want to investigate the effect
      of mineralocorticoid receptor antagonists in type 2 diabetes patients on myocardial function,
      glucose and fat metabolism.

      Background The mortality rate in T2 DM is still increased by almost a factor 2 although poly
      pharmacological therapy of risk factors has been recommended for years. Treatment with MR
      antagonists in patients with primary hyperaldosteronism and systolic heart failure improves
      insulin resistance, myocardial function and prognosis. Further, recent evidence has suggested
      that aldosterone participates in the regulation of glucose and lipid metabolism, as MR
      expression has been identified in adipocytes and beneficial metabolic effects of selective MR
      blockade has been demonstrated in several animal models. Notably, there is no available data
      in humans with T2DM.

      A key feature of T2 DM is altered body composition characterized by increased metabolic
      active visceral adipose tissue (VAT) and increased fat content of the liver, which has been
      associated with cardiac dysfunction and outcome. Gold standard for measurement of VAT is
      magnetic resonance imaging (MRI), and proton MRI spectroscopy can quantitatively measure fat
      content in the liver with high precision. The pathogenesis of myocardial dysfunction in T2DM
      is linked with insulin resistance (IR) of adipose tissue mediating increased supply of free
      fatty acids and intra myocardial lipid accumulation. Thus, beneficial effects of lipid
      metabolism could in theory indirectly improve myocardial function in type 2 diabetics.

      Global longitudinal strain (GLS) is a validated method for evaluating regional and global
      function of the left ventricle, which is a strong predictor of incident HF in patients with
      myocardial infarction and closely related with plasma NT-proBNP concentrations.

      Hypothesis Selective blocking of the MR receptor in patients with T2 DM improves insulin
      resistance, lipid metabolism and myocardial function.

      Objectives To investigate the effect of Eplerenone 100-200 mg once daily compared to placebo
      in patients with type 2 diabetes with regard to glucose and lipid metabolism, myocardial
      function and structure, and vascular function.

      The primary objective is to investigate the effect of Eplerenone 100-200 mg once daily
      compared to placebo on changes in liver fat content.

      Design A single center, randomized, double blinded placebo controlled trial. Patients with T2
      DM and high risk of cardiovascular disease will be randomized to either Eplerenone 100-200 mg
      or placebo daily for 26 weeks. Patients will be investigated at baseline and after 26 weeks.

      A total of 130 patients with type 2 diabetes will be included.
    

Intervention name(s): Eplerenone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 50 mg tablets, oral use.; 50 mg tablets, oral use
Intervention MeSH terms: Eplerenone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment