After a meal, incretin hormones are released from cells in the intestines. GLP-1, a 30 amino acid peptide, binds to GLP-1 receptors found in the GI tract, pancreas, brain, heart, and kidneys. Unlike GLP-1, GIP receptors are highly expressed on adipocytes. GIP is a 42 amino acid peptide. A major effect of GLP-1 and GIP is to stimulate insulin secretion, contributing to the incretin effect. In type 2 diabetes, the incretin effect is reduced. Tirzepatide is an emerging 39 amino acid synthetic peptide with a 5-day half-life, allowing for once-weekly dosing. It is a dual GIP/GLP-1 receptor agonist, having agonist activity at both the GIP and GLP-1 receptors, with greater affinity to GIP receptors. This synergy may result in a greater effect on glucose levels and body weight in patients with type 2 diabetes.
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