Management of Diabetes With Metformin In Patients With Chronic Heart Failure

• ClinicalTrials.gov Identifier: NCT01122316
• Recruitment Status: Completed
• First Posted: May 13, 2010
• Results First Posted: September 4, 2020
• Last Update Posted: September 4, 2020
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Tamara Horwich, University of California, Los Angeles

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Heart Failure; Diabetes	Drug: Metformin	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Management of Diabetes With Metformin In Patients With Chronic Heart Failure
• Study Start Date: September 2009
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: January 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Metformin	Drug: Metformin; 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.

Outcome Measures

Primary Outcome Measures :

1. Health-Related Quality of Life (HRQoL) [ Time Frame: 3 months ]

   HRQoL as assessed by the Minnesota Living With Heart Failure Questionnaire (MLHFQ)

   The MLHFQ is a self-administered questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on HRQoL, from 0 (none) to 5 (very much). It provides a total score range 0-105. Lower scores indicate better health-related quality of life (HRQoL).

Secondary Outcome Measures :

1. Glycated Hemoglobin (HbA1c) [ Time Frame: 3 months ]
   The HbA1c test measures how much glucose is bound to hemoglobin in the red blood cells. The test shows the average level of glucose in blood for the past 3 months (the average lifespan of red blood cells). If glucose levels have been high over recent weeks, the hemoglobin A1c test will be higher.
2. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 3 months ]
   Obtained from Echocardiography
3. Creatinine Level as a Measure of Renal Function [ Time Frame: 3 months ]
   Serum creatinine

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Systolic HF of any etiology (left ventricular ejection fraction ≤ 40%)
• Previously-diagnosed, inadequately controlled DM (HbA1c≥7.5%)
• On any combination of anti-diabetic medications excluding metformin

Exclusion Criteria:

• Current metformin therapy
• Previous intolerance to metformin therapy
• Renal dysfunction (creatinine clearance < 60 ml/minute)
• History of lactic acidosis.

Contacts and Locations

Locations

United States, California

Ahmanson-UCLA Cardiomyopathy Center

Los Angeles, California, United States, 90095-7368

Sponsors and Collaborators

University of California, Los Angeles

Investigators

• Principal Investigator: Tamara Horwich, MD, MS; University of California, Los Angeles

More Information

• Responsible Party: Tamara Horwich, Tamara Horwich, MD, MS, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01122316
• Other Study ID Numbers: 09-06-086-02
• First Posted: May 13, 2010
• Results First Posted: September 4, 2020
• Last Update Posted: September 4, 2020
• Last Verified: August 2020

Keywords provided by Tamara Horwich, University of California, Los Angeles:

Heart Failure; Diabetes; Metformin

Additional relevant MeSH terms:

Heart Failure; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs