The Influence of Metformin on Chronic Heart Failure Clinical Course in Patients With Prediabetes
Condition: Chronic Heart Failure; Coronary Artery Disease; PreDiabetes
MeSH terms: Heart Failure; Coronary Artery Disease; Prediabetic State; Glucose Intolerance; Disease Progression
Study type: Interventional
Phase: Phase 4

Summary: 
      It is well known fact, that prediabetes is a predictor of high cardiovascular mortality,
      increasing the risk of developing such adverse cardiovascular events as myocardial
      infarction, stroke and sudden cardiac death. The key pathogenetic link in development of
      carbohydrates metabolism disorders (CMD) is insulin resistance (IR), which is one of the
      crucial mechanisms for the development and progression of chronic heart failure (CHF). IR
      disrupts the functioning of the myocardium due to endothelial dysfunction, inflammation,
      oxidative stress, remodeling and impaired myocardial metabolism. In condition of a
      combination of CMD and CHF the reverse development of hyperglycemia is also difficult due to
      hyperactivation of neurohormonal systems - renin-angiotensin-aldosterone system, in
      particular.

      So, drug therapy should neutralize the undesirable metabolic effects of hyperglycemia on the
      course of CHF, as well as prevent the development of micro- and macrovascular complications.

      The study will investigate the ability of metformin to impact on clinical and laboratory
      (neurohormonal, lipid profiles, renal function) parameters of ischemic etiology heart failure
      patients with prediabetes, as well as their quality of life and prognosis (incidence of
      adverse cardiovascular events). These tests will be assessed at the beginning and repeated
      after one year. At the end of the study we will investigate the difference between lifestyle
      modification effect and metformin treatment.

      The study is funded by Ministry of Education and Science of Kyrgyz Republic.
    

Detailed description: 
      This is a single centre trial designed to investigate the benefit, if any, of 12-month
      metformin 2000 mg/day treatment on clinical course of chronic heart failure in 78 patients
      with coronary artery disease and impaired glucose tolerance.

      Participants will be seen in three occasions: screening, baseline randomization, 6 month,
      final 12 month, during which clinical and laboratory indicators will be assessed. There will
      also be three telephone visits at: month 1, month 3, month 9.

      At a screening visit an initial history will be performed during following informed consent.
      Participants will undergo a laboratory, clinical and instrumental screening in Chronic Heart
      Failure department of National Centre of cardiology and Internal Medicine named after
      academician M.Mirrakhimov. Among with anthropologic and clinical data, prior to metformin
      administration, blood samples were evaluated.

      Participants who meet all inclusion criteria will return for the randomization during
      hospitalization to either Metformin or Lifestyle modification alone.

      After 6 months of observation safety indicators will be evaluated, as well as fasting and
      postprandial glucose, creatinine, ECG.

      In the active arm, therapy will be metformin in an initial dose of 1000 mg/day (metformin 500
      mg х2/day). Participants will continue on Metformin 500 mg x2/day for 2 weeks, following
      safety blood checks this dose will be increased to 2000 mg/day. If the higher dose cannot be
      tolerated it will be reduced to 1000 mg/day (or stopped if not tolerated).

      The target dose of Metformin at 2000 mg/day was chosen based on previous study of metformin
      in nondiabetic heart failure patients with IR
    

Intervention name(s): Metformin Hydrochloride; lifestyle modification
Intervention type(s): Drug; Other
Intervention description(s): patients were divided into 2 groups: 1st group was on lifestyle modification (LSM), 2nd group on regimen "LSM+ metformin (1000 g b.i.d)" during 12 months; Lifestyle modification Standard Principles
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: metformin; chronic heart failure; prediabetes; insulin resistance; clinical course