Examining the Impact of Old and New Antidiabetic Agents on Heart Failure
Diabetes mellitus (DM) and heart failure (HF) are common coexisting conditions.1 As many as one quarter to one third of patients with HF also have DM, and DM is an independent predictor of the development and progression of HF.1 The mechanism by which DM adversely affects HF is via myocardial insulin resistance.2-4 Additionally, hyperglycemia is associated with neurohormonal activation, inflammatory cytokines, reactive oxygen species, and oxidative stress, resulting in endothelial dysfunction and hemodynamic impairment.1 It is possible that there is a disease-specific diabetic cardiomyopathy that is independent of other risk factors.1 Thus, the pathogenesis of HF in DM is “multifactorial, with contributions from coronary artery disease (CAD), hypertension, diabetic cardiomyopathy, and extracellular volume expansion.”1
Poor glycemic control is associated with an increased risk of HF; however, certain medications used to treat hyperglycemia may not reduce and may actually increase the risk of HF.1 A recent article by DeFilippis and Givertz1 examines the impact of both older and newer antidiabetic medications on HF.
Older Medications: Thiazolidinediones and Metformin
The thiazolidinediones (TZDs) have been associated with increased risk of HF. In 2003, the American Heart Association (AHA) and the American Diabetes Association (ADA) issued a consensus statement5 cautioning against the use of thiazolidinediones (TZDs) in patients with New York Heart Failure (NYHA) classes III and IV HF because several randomized trials of these agents were shown to increase cardiovascular risk. Even in patients who are asymptomatic or have only mild symptoms, these agents should be used cautiously and initiated at low doses and with careful monitoring.5
In the context of worsening HF, especially in patients with concomitant renal dysfunction, metformin—usually the cornerstone of DM therapy—can lead to excessive diuresis, altered renal blood flow and possibly lactic acidosis.1 However, a substantial body of evidence suggests that metformin actually reduces mortality in patients with DM and HF.1