Wrongfully Accused: Metformin Use in Heart Failure
Metformin has long been the cornerstone of therapy for glycemic control in patients with Type 2 diabetes worldwide. It is recommended as first-line therapy by all major diabetes clinical practice guidelines owing to its efficacy, favorable tolerability profile and beneficial effects in limiting weight gain. Moreover, metformin is the only oral anthyperglycemic agent shown in randomized controlled trials to reduce mortality in newly diagnosed patients with Type 2 diabetes. However, the use of metformin has not been without controversy, in particular in patients with heart failure. This article will review a recent observational study by Aguilar et al. published in Circulation – Heart Failure that reported improved outcomes associated with metformin therapy in patients with diabetes and heart failure.
Heart failure is a very common comorbidity present in 25–40% of all adults with diabetes. Diabetes also portends poorer outcomes in patients with heart failure and hyperglycemia is associated with increased risk of hospital admission. Historically, the use of metformin in patients with comorbid heart failure was considered 'absolutely' contraindicated owing to the perceived increased risk of lactic acidosis. Recently, regulatory bodies in both Canada (Health Canada) and the USA (US FDA) have removed the heart failure contraindication from product labeling for metformin, although a 'black box' warning for the cautious use of metformin in this population still exists. How best to control blood glucose in patients with diabetes and heart failure still remains controversial owing to the lack of randomized controlled trial evidence. Indeed, except for one small randomized controlled trial (n = 222), patients with heart failure have been excluded from trials of glucose-lowering therapies.
Not surprisingly, there is increasing reliance on observational studies to address the evidence gap that currently exists with the majority of these studies focusing on the role of metformin. Previous studies have routinely indicated a substantial reduction in mortality and/or hospitalization associated with metformin therapy. However, given the nature of these studies, differences between the antihyperglycemic drug classes may be the result of residual confounding or selection bias as few studies have included prognostic information important in diabetes and heart failure. The latest observational study published in Circulation – Heart Failure evaluating the effects of metformin in a national cohort of ambulatory patients with diabetes and established heart failure adds to this growing body of evidence and is the subject of this evaluation.
Abstract and Introduction
Abstract
Metformin has long been the cornerstone of therapy for glycemic control in patients with Type 2 diabetes worldwide. It is recommended as first-line therapy by all major diabetes clinical practice guidelines owing to its efficacy, favorable tolerability profile and beneficial effects in limiting weight gain. Moreover, metformin is the only oral anthyperglycemic agent shown in randomized controlled trials to reduce mortality in newly diagnosed patients with Type 2 diabetes. However, the use of metformin has not been without controversy, in particular in patients with heart failure. This article will review a recent observational study by Aguilar et al. published in Circulation – Heart Failure that reported improved outcomes associated with metformin therapy in patients with diabetes and heart failure.
Introduction
Heart failure is a very common comorbidity present in 25–40% of all adults with diabetes. Diabetes also portends poorer outcomes in patients with heart failure and hyperglycemia is associated with increased risk of hospital admission. Historically, the use of metformin in patients with comorbid heart failure was considered 'absolutely' contraindicated owing to the perceived increased risk of lactic acidosis. Recently, regulatory bodies in both Canada (Health Canada) and the USA (US FDA) have removed the heart failure contraindication from product labeling for metformin, although a 'black box' warning for the cautious use of metformin in this population still exists. How best to control blood glucose in patients with diabetes and heart failure still remains controversial owing to the lack of randomized controlled trial evidence. Indeed, except for one small randomized controlled trial (n = 222), patients with heart failure have been excluded from trials of glucose-lowering therapies.
Not surprisingly, there is increasing reliance on observational studies to address the evidence gap that currently exists with the majority of these studies focusing on the role of metformin. Previous studies have routinely indicated a substantial reduction in mortality and/or hospitalization associated with metformin therapy. However, given the nature of these studies, differences between the antihyperglycemic drug classes may be the result of residual confounding or selection bias as few studies have included prognostic information important in diabetes and heart failure. The latest observational study published in Circulation – Heart Failure evaluating the effects of metformin in a national cohort of ambulatory patients with diabetes and established heart failure adds to this growing body of evidence and is the subject of this evaluation.
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