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Management of Diabetes With Metformin In Patients With Chronic Heart Failure

Management of Diabetes With Metformin In Patients With Chronic Heart Failure

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01122316
Enrollment
10
Registered
2010-05-13
Start date
2009-09-30
Completion date
2012-01-31
Last updated
2020-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes, Heart Failure

Keywords

Heart Failure, Diabetes, Metformin

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.

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.

Interventions

DRUGMetformin

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.

Sponsors

University of California, Los Angeles
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Health-Related Quality of Life (HRQoL)3 monthsHRQoL 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

MeasureTime frameDescription
Glycated Hemoglobin (HbA1c)3 monthsThe 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.
Left Ventricular Ejection Fraction (LVEF)3 monthsObtained from Echocardiography
Creatinine Level as a Measure of Renal Function3 monthsSerum creatinine

Countries

United States

Participant flow

Participants by arm

ArmCount
Metformin
Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
10
Total10

Baseline characteristics

CharacteristicMetformin
Age, Continuous52.5 years
STANDARD_DEVIATION 10
Race and Ethnicity Not Collected— Participants
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
8 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
0 / 10
serious
Total, serious adverse events
0 / 10

Outcome results

Primary

Health-Related Quality of Life (HRQoL)

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).

Time frame: 3 months

Population: Analysis includes participants who completed intervention and final study assessment

ArmMeasureGroupValue (MEAN)Dispersion
MetforminHealth-Related Quality of Life (HRQoL)Baseline56 score on a scaleStandard Deviation 25
MetforminHealth-Related Quality of Life (HRQoL)Three Months53 score on a scaleStandard Deviation 35
Secondary

Creatinine Level as a Measure of Renal Function

Serum creatinine

Time frame: 3 months

Population: Analysis includes participants who completed intervention and final study assessment

ArmMeasureGroupValue (MEAN)Dispersion
MetforminCreatinine Level as a Measure of Renal FunctionBaseline1.04 mg/dLStandard Deviation 0.18
MetforminCreatinine Level as a Measure of Renal FunctionThree Months1.09 mg/dLStandard Deviation 0.2
Secondary

Glycated Hemoglobin (HbA1c)

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.

Time frame: 3 months

Population: Analysis includes participants who completed intervention and final study assessment

ArmMeasureGroupValue (MEAN)Dispersion
MetforminGlycated Hemoglobin (HbA1c)Baseline9.1 percentage of glycated hemoglobinStandard Deviation 2.3
MetforminGlycated Hemoglobin (HbA1c)Three Months8.9 percentage of glycated hemoglobinStandard Deviation 3
Secondary

Left Ventricular Ejection Fraction (LVEF)

Obtained from Echocardiography

Time frame: 3 months

Population: Analysis includes participants who completed intervention and final study assessment

ArmMeasureGroupValue (MEAN)Dispersion
MetforminLeft Ventricular Ejection Fraction (LVEF)Baseline22 percent ejection fractionStandard Deviation 11
MetforminLeft Ventricular Ejection Fraction (LVEF)Three Months28 percent ejection fractionStandard Deviation 11

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026