Glucagon-like peptide-1 agonists

Over the past century, considerable progress has been made in understanding the role of enteroendocrine signals in regulating glucose. One substantial advance was the delineation of the “the incretin effect,” which refers to the ability of orally administered glucose to stimulate pancreatic insulin secretion to a greater extent than glucose administered intravenously.1 Glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide are the two key enteroendocrine factors responsible for the incretin effect.2 GLP-1, secreted from the lower gastrointestinal tract L-cells after nutrient ingestion, stimulates endogenous insulin secretion in a glucose dependent manner, inhibits postprandial glucagon release, delays gastric emptying, and increases satiety.3 However, GLP-1 is of limited therapeutic use because it is rapidly degraded by dipeptidyl peptidase 4, an enzyme produced at epithelial and endothelial membranes.

In the linked systematic review and meta-analysis (doi:10.1136/bmj.d7771), Vilsbøll and colleagues assess the effect of GLP-1 receptor agonists on weight loss, blood pressure, plasma concentrations of cholesterol and liver enzymes, and glycaemic control.4 The two currently approved GLP-1 analogues, exenatide and liraglutide, mimic the action of GLP-1 but are resistant to the proteolytic …