Management of Diabetes With Metformin In Patients With Chronic Heart Failure

2014-08-27 03:13:46 | BioPortfolio


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 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.


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 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 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.


1. Heart Disease and Stroke Statistics - 2005 update. American Heart Association.

2. Horwich TB, Fonarow GC. Impact and Treatment of Comorbidities in Heart Failure. In: Hosenspud JD, Greenberg BH, eds. Congestive Heart Failure Third ed. Philadelphia: Lippincott Williams and Wilkins, 2007:670-681.

3. Gustafsson I, Brendorp B, Seibaek M, et al. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. J Am Coll Cardiol 2004;43:771-7.

4. Smooke S, Horwich TB, Fonarow GC. Insulin-treated diabetes is associated with a marked increase in mortality in patients with advanced heart failure. Am Heart J 2005;149:168-74.

5. Held C, Gerstein HC, Yusuf S, et al. Glucose Levels Predict Hospitalization for Congestive Heart Failure in Patients at High Cardiovascular Risk. Circulation 2007;115:1371-1375.

6. Gebreegziabher Y, McCullough PA, Bubb C, et al. Admission hyperglycemia and length of hospital stay in patients with diabetes and heart failure: a prospective cohort study. Congest Heart Fail 2008;14:117-20.

7. Berry C, Brett M, Stevenson K, McMurray JJV, Norrie J. Nature and prognostic importance of abnormal glucose tolerance and diabetes in acute heart failure. Heart 2008;94:296-304.

8. Swan JW, Anker SD, Walton C, et al. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 1997;30:527-32.

9. Suskin N, McKelvie RS, Burns RJ, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J 2000;21:1368-1375.

10. Eurich DT, McAlister FA, Blackburn DF, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review. Bmj 2007;335:497.

11. Inzucchi SE, Masoudi FA, McGuire DK. Metformin in Heart Failure. Diabetes Care 2007;30:e129-.

12. Masoudi FA, Wang Y, Inzucchi SE, et al. Metformin and thiazolidinedione use in Medicare patients with heart failure. Jama 2003;290:81-5.

13. Shah DD FG, Horwich TB. Metformin therapy in advanced, systolic heart failure patients with diabetes is associated with improved survival and improved cardiac function. Circulation 2008;118:S717.

14. Bell DS. Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 2003;26:2433-41.

15. Kostis JB, Sanders M. The Association of Heart Failure With Insulin Resistance and the Development of Type 2 Diabetes[ast]. Am J Hypertens 2005;18:731.

16. Grant PJ. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care 1996;19:64-6.

17. Kawabata H, Ishikawa K. Cardioprotection by metformin is abolished by a nitric oxide synthase inhibitor in ischemic rabbit hearts. Hypertens Res 2003;26:107-10.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Heart Failure




Ahmanson-UCLA Cardiomyopathy Center
Los Angeles
United States




University of California, Los Angeles

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:13:46-0400

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Medical and Biotech [MESH] Definitions

A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.

Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.

Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying.

Heart failure caused by abnormal myocardial relaxation during DIASTOLE leading to defective cardiac filling.

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