Incretins are gut hormones that are secreted from the enteroendocrine cells into the blood within minutes after eating. The insulin secretory response of incretins, called the incretin effect. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase- 4 (DPP-4). Mimicking or enhancing the actions of incretin can help to control type 2 diabetes. Exenatide and liraglutide are injectable GLP-1 receptor agonists (GLP-1R), while vildagliptin and sitagliptin are oral DPP-4 inhibitors. GLP-1R agonists lower glycated haemoglobin by about 0.6--1% and induce weight loss. DPP-4 inhibitors reduce glycated haemoglobin by 0.5--0.8% and have no effect on weight. The GLP-1--related drugs arrived in clinical practice with much fanfare and anticipation. DPP- 4 enzyme is a ubiquitous cell-membrane protein, expressed in many tissues, including lymphocytes, which has raised some concerns about the long-term effects of DPP-4 inhibitors, especially on immune function. Data consistent with case reports and animal studies indicate an increased risk for pancreatitis with GLP-1-based therapy and also raise caution about the potential long-term actions of these drugs to promote pancreatic and thyroid cancers. This lecture will review the incretin-based therapies with focus on their benefits and their potential transient and serious side effects.
