Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Glucagon-like Peptide-1 Receptor Agonists

Coincident with the diabetes pandemic, diabetic complications—especially kidney disease and cardiovascular disease—have become large-scale public health problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, a newer class of anti-hyperglycemic therapies, represent a major advance in the treatment of these complications in type 2 diabetes. In addition to effectively treating hyperglycemia, they have a low intrinsic risk of hypoglycemia and promote reductions in blood pressure and body weight. Furthermore, in clinical trials of GLP-1 receptor agonists, the risks of cardiovascular events and new or worsening diabetic kidney disease (DKD) were reduced. As a result, guidelines from major professional organizations now recommend GLP-1 receptor agonists for patients with type 2 diabetes, to reduce the risk of atherosclerotic cardiovascular disease or DKD. The exact mechanism behind these clinical benefits is currently under investigation, as they cannot be fully explained by the observed glycemic-lowering properties, or the modest improvements in blood pressure and weight loss caused by agents in this class. Emerging data suggest that the pro-inflammatory consequences of diabetes are a likely therapeutic target for the immunomodulatory effects of GLP-1 receptor agonists on the kidney and heart