Coronary Artery Disease Progression in Patients With Prediabetes
Condition: Coronary Artery Disease; Atherosclerosis; Prediabetic State
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis; Prediabetic State; Glucose Intolerance; Disease Progression
Study type: Interventional
Phase: Phase 4

Summary: 
      Prediabetes is a disorder of glucose metabolism that reflects the natural history of
      progression from normoglycaemia to type 2 diabetes mellitus. Patients with prediabetes have
      impaired glucose regulation caused by insulin resistance (IR). IR in patients undergoing
      percutaneous coronary intervention (PCI) is associated with coronary artery remodeling and
      coronary plaque vulnerability by intravascular ultrasound (IVUS) analysis. In stent
      restenosis after bare metal and drug-eluting stent implantation more frequently is observed
      in patients with high fasting-insulin levels and IR. Although IR has a significant role in
      the progression of atherosclerosis in prediabetic patients, the importance of managing
      prediabetes is often under-appreciated by clinicians. To date, no pharmacological treatment
      has been officially approved for prediabetes. According to American Diabetes Association
      recommendations, metformin is the only drug that could be considered in the treatment of
      prediabetic patients with a high risk of developing diabetes. Metformin is a safe and
      inexpensive glucose lowering drug that attenuates mortality and future cardiovascular events
      in patients with type 2 diabetes as well as the progression of atherosclerosis in
      non-diabetic animal models. This study was designed to analyze coronary plaque
      characteristics by iMAP IVUS in patients with and without prediabetes undergoing PCI and to
      evaluate the impact of metformin treatment on coronary plaque characteristics in prediabetic
      patients at 24 month follow up.

      The study hypothesis is that more pronounced coronary atherosclerosis progression as well as
      in-stent neointimal hyperplasia will be observed in patients with prediabetes. Metformin
      treatment attenuates the progression of atherosclerosis in patients with prediabetes.
    

Detailed description: 
      Patients undergoing PCI and IVUS pullback for the target vessel will be enrolled in a
      prospective study. Before PCI and at 24 month follow up fasting blood will be collected for
      glucose, HbA1c, C peptide, lipid profile assessment. Patients' baseline demographic
      characteristics, medical history, and procedural data will be collected during the index
      hospitalization and at 24 month follow up. Patients will be divided in groups according to
      HbA1c - control group (HbA1c<5.7) and prediabetic patients (HbA1c 5.7-6.4). PCI will be
      performed in accordance with the guidelines. After successful treatment of the culprit lesion
      IVUS will be done. Following PCI and IVUS patients with prediabetes will be randomly assigned
      in groups either receiving metformin at a dose of 2000 mg once daily plus standard lifestyle
      recommendations or standard lifestyle recommendations only. Intravascular ultrasound analysis
      will be repeated 24 months after the initial PCI.
    

Intervention name(s): Metformin; Lifestyle recommendations
Intervention type(s): Drug; Behavioral
Intervention description(s): In order to minimize gastrointestinal discomfort, metformin treatment will be started with a dose of 500 mg p/o once daily, then gradually increased to 2000 mg p/o once daily for 24 months; Standard lifestyle recommendations
Other intervention name(s): Glucophage extended release (XR)
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Coronary artery disease; Atherosclerosis; Prediabetes; Intravascular ultrasound; Insulin resistance; Percutaneous coronary intervention; Metformin