Managing diabetes mellitus is an ongoing concern, especially in the presence of heart failure. Recent reports have drawn attention to adverse cardiovascular events associated with the use of thiazolidinediones, including rosiglitazone (Avandia). In 2011, the U.S. Food and Drug Administration implemented a stringent "restricted access program" for the prescription of Avandia. Other studies, which have revealed increased mortality rates in association with tight glycemic control, raise serious concerns about managing diabetes in heart-failure patients. Herein, we provide a perspective on the management of noninsulin-dependent diabetes in patients with heart failure. We point out that thiazolidinediones exert their major effects through insulin sensitization, which potentiates the action of insulin. A defining feature of insulin resistance is excess fuel supply and restricted rates of substrate utilization by the heart. We postulate that the use of excess insulin and insulin-sensitizing agents can lead to adverse cardiovascular events and contractile dysfunction through an increase of substrate uptake to an insulin-resistant heart that is already flooded with fuel. We include a table of antidiabetic agents and nonpharmacologic interventions aimed at lowering substrate supply, and of the respective clinical trials supporting their safety and efficacy. Although previously contraindicated in patients with heart failure, metformin appears to be both safe and effective therapy for diabetes in those patients. Because metformin reduces gluconeogenesis in the liver, we propose that the management of diabetes in heart-failure patients should target the source, rather than the destination, of excess fuel.
Keywords: Cardiovascular diseases/mortality/prevention & control; diabetes mellitus, type 2/complications/drug therapy/mortality; heart failure, systolic/chemically induced; hypoglycemic agents/administration & dosage; insulin resistance/physiology; metformin/pharmacology/therapeutic use; randomized controlled trials as topic; risk assessment; rosiglitazone; thiazolidinediones/adverse effects.