Metformin Use in Patients With Diabetes and Heart Failure: Cause for Concern?

Abstract

Patients with type 2 diabetes are 2.5 times more likely to develop heart failure than those without diabetes,1 and > 30% of patients with heart failure have concurrent diabetes.2 Biguanides, namely phenformin and metformin, have been used for the treatment of diabetes for decades. In certain clinical situations, however, the use of biguanides can result in an accumulation of lactic acid, which may result in a rare condition known as acute lactic acidosis (ALA), which is fatal in ∼ 50% of cases.3,4 In most instances, the development of ALA arises secondary to conditions predisposing patients to hemodynamic compromise and overt tissue hypoxia, such as acute myocardial infarction (MI), acute uncompromised heart failure, or sepsis.5,6 Phenformin was removed from the market in 1976 because of reports of both fatal and nonfatal phenformin-associated lactic acidosis (PALA).7 The incidence of PALA at the time was estimated to be between 40 and 64 cases per 100,000 patient-years, or four to six times that seen in patients with diabetes who were not on phenformin.8,9 Unlike phenformin, which is metabolized through the liver via hydroxylation, metformin is excreted unchanged in the urine.10 Therefore, metformin is less likely to inhibit hepatic lactate clearance and lead to ALA. The estimated incidence of metformin-associated lactic acidosis (MALA) in patients with diabetes is between 3 and 9 cases per 100,000 patient-years, roughly the same as that reported in patients with diabetes who are not taking a biguanide.4,7,11–13 Epidemiological data reveal that metformin is often used in patients with heart failure. Prospective and retrospective cohort studies have evaluated health care databases of hospitalized and outpatient diabetic populations to determine metformin usage in patients with concurrent International Classification of Diseases-9 (ICD-9) codes …