The Cardiovascular Benefits of Glucagon-like Peptide-1 (GLP-1) Receptor Agonists

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were initially approved by the Food and Drug Administration to improve glycemic control in patients with type 2 diabetes (T2DM). However, their use was associated with a significant weight loss benefit, subsequently leading to their Food and Drug Administration approval for use in obesity and select overweight patients with or without T2DM. Additionally, as part of regulatory clinical trials required for approval of all antidiabetic medications, GLP-1 RAs were discovered to have significant cardiovascular benefits beyond their glycemic control and weight loss properties. Multiple cardiovascular outcome trials demonstrated that GLP-1 RAs cause a significant reduction in major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, in patients with T2DM. The proposed mechanisms of action responsible for GLP-1 RAs cardiovascular benefits include their improvement in glycemic control, substantial weight loss effect, modest reduction in blood pressure, antiatherosclerotic effect, and anti-inflammatory effect. Additionally, with the increase in the heart failure (HF) epidemic worldwide, researchers have begun investigating whether GLP-1 RAs may have a role in the treatment of HF with reduced or preserved ejection fraction in patients with or without T2DM. However, early, small, underpowered clinical trials on this topic have yielded varying results and were unable to clearly identify the role of GLP-1 RAs in the treatment of HF. There is a growing need for a large clinical trial to investigate and establish the safety and efficacy of GLP-1 RAs in HF patients with and without T2DM.