Dual Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Receptor Agonists

Abstract

Glucagon-like peptide-1 is the most potent incretin secreted from the intestinal tract. It is synthesized by L-cells in the jejunum and distal ileum of the gastrointestinal system. Glucose-dependent insulinotropic polypeptide is a polypeptide released by specialized endocrine cells called K cells, most commonly in the duodenum and jejunum, in response to oral food, especially carbohydrates and lipids. Glucose-dependent insulinotropic polypeptide receptors are found in various tissues such as adipose tissue, gastric mucosa, adrenal cortex, pancreas, bone, heart, and brain. The long-term effect of GIP and Glucagon-like peptide-1 receptor agonism was first demonstrated by Finan et al. They have developed a single-molecule dual Glucose-dependent insulinotropic polypeptide and Glucagon-like peptide-1 receptor agonist called “Twincretin.” Twincretin has been shown to have negligible glucagon receptor activity and a high affinity for Glucagon-like peptide-1 and Glucose-dependent insulinotropic polypeptide receptors. Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist currently under trial to evaluate glycemic efficacy and safety in people with type 2 diabetes, non-alcoholic steatohepatitis, and obesity. Tirzepatide significantly improved glycemic control and body weight and had an acceptable safety profile, this indicates that it is an effective therapeutic option for glucose lowering in patients with type 2 diabetes.