Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure

Abstract

Metformin has been in clinical use for the management of type 2 diabetes for more than 60 years and is supported by a vast database of clinical experience: this includes evidence for cardioprotection from randomised trials and real-world studies. Recently, the position of metformin as first choice glucose-lowering agent has been supplanted to some extent by the emergence of newer classes of antidiabetic therapy, namely the sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. These agents have benefitted through support from large cardiovascular outcomes trials with more modern trial designs than earlier studies conducted to assess metformin. Nevertheless, clinical research on metformin continues to further assess its many potentially advantageous effects. Here, we review the evidence for improved cardiovascular outcomes with metformin in the context of the current era of diabetes outcomes trials. Focus is directed towards the potentially cardioprotective actions of metformin in patients with type 2 diabetes and heart failure (HF), now recognised as the most common complication of diabetes.