Management of Diabetes With Metformin In Patients With Chronic Heart Failure
Condition: Heart Failure; Diabetes
MeSH terms: Heart Failure; Diabetes Mellitus
Study type: Interventional

Summary: 
      The Ahmanson-UCLA Cardiomyopathy Center is conducting a clinical research study that will
      assess the use of the medication metformin to improve quality of life, exercise capacity, and
      improved outcomes with patients that have both heart failure and diabetes.

      If you participate in this study, you will receive the drug metformin for approximately 3
      months. During the study you will undergo comprehensive testing which includes blood draws,
      an echocardiogram, and an magnetic resonance imaging (MRI)(if you do not have a pacemaker or
      defibrillator). You will also fill out a questionnaire and keep a blood glucose log.

      You must be 18 years old to participate. The study drugs, study follow-up visits, and
      laboratory tests will be provided free of charge. Participants will be reimbursed up to $200
      for their time and travel expenses.
    

Detailed description: 
      Heart failure (HF) affects 5 million individuals in the United States including over 10% of
      elderly persons >75 years. HF mortality is high, with approximately 20% 1-year risk of death
      (1). Diabetes (DM) is a common co-morbidity in patients with HF, present in approximately 25%
      of stable outpatients and 40% of hospitalized patients with HF (2). Diabetes in HF patients
      is associated with higher mortality (3,4). Hyperglycemia is independently associated with
      hospitalization for HF, longer length of stay during HF hospitalization, as well as higher
      in-hospital HF mortality (5-7). Furthermore, HF patients with more symptoms and worse
      functional status are more likely to have insulin resistance (8,9).

      Despite the abundance of evidence linking diabetes, insulin resistance, and hyperglycemia to
      impaired functional status and worse outcomes in patients with HF, there is lack of data and
      guidelines on optimal strategies to manage diabetes in patients with chronic HF. In
      retrospective studies, many diabetes medications in HF have been associated with harm
      including insulin, thiazolidinediones, and sulfonylureas (10). The only anti-hyperglycemic
      medication that has been associated in retrospective studies with benefit in patients with HF
      and diabetes is metformin, which recently had its "black box warning" in HF lifted by the
      FDA, although most physicians are unaware of the change in labeling (10-12). Our analysis of
      data on 401 advanced, systolic HF patients with DM followed at the Ahmanson-UCLA
      Cardiomyopathy Center also found metformin therapy to be associated with improvement of left
      ventricular ejection fraction (LVEF) as well as decreased 1-year mortality (figure 1)(13).

      Glycemic control in HF patients has not been prospectively studied; however, improved
      glycemic control has potential benefits in HF, including improvement of myocardial glucose
      utilization, decrease of potentially cardiotoxic free fatty acids, and reduced accumulation
      of myocardial collagen and advanced glycation end-products (14,15). Metformin therapy,
      compared to insulin and other antidiabetic medications, has potentially beneficial mechanisms
      of action in HF including insulin sensitization, improvement in lipid profiles, and more
      efficient myocardial metabolism (16,17). The purpose of this study is to gather pilot data
      for an anticipated comprehensive study DM management in HF, with the goal of NIH funding.
    

Intervention name(s): Metformin
Intervention type(s): Drug
Intervention description(s): 3. Metformin will be started at 500 mg PO BID and pending lab values may be titrated to 1000 mg PO BID at 1 month.
Intervention MeSH terms: Metformin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Heart Failure; Diabetes; Metformin