Evidence from randomized clinical trials demonstrating improved glycemic control with GLP-1 receptor agonists when used with other agents vs other combination therapy strategies

Incretin-based therapies include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) based therapies. Both classes of agents are predicated on the knowledge that GLP-1, a gut-derived hormone, plays a major role in glucose homeostasis, a fact that has been known for several decades; however, until recently GLP-1 has not been able to be harnessed into a pharmacologically viable target with which to treat type 2 diabetes. GLP-1 receptor agonists (GLP-1 RA) provide supraphysiologic levels of GLP-1, resulting in increased levels of insulin and decreased glucagon secretion, without attendant hypoglycemia risk or risk of weight gain. They are more potent than DPP-4 inhibitors, may result in weight loss, have different adverse effect profiles, and may have other different pharmacological nonglycemic effects than DPP-4 inhibitors. They can be successfully used as part of combination therapy strategies, which is important because type 2 diabetes has multiple pathophysiological defects that need to be addressed to successfully maintain or achieve glucose goals.