Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features

Glucagon-like peptide-1 receptor analogues/agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stimulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress glucagon release in a glucose-dependent manner, thereby improving clinical and patient-reported outcomes related to glycaemic control and weight. They also have been shown to reduce, or at least not increase, the risk of major cardiovascular outcomes. GLP-1RAs are generally well tolerated, with gastrointestinal and injection-site reactions being the most troublesome drug-related adverse events, and are associated with a very low intrinsic risk of hypoglycaemia. Treatment with GLP-1RAs should be customized to meet the clinical needs and personal preferences of the individual.