GIP is released by K cells in the duodenum and proximal jejunum, mainly in response to fat and glucose. Together with GLP-1 it is responsible for the incretin effect, and in healthy people its contribution to post-meal insulin is even larger than that of GLP-1.
Besides the pancreas, its receptor (GIPR) is found in adipose tissue and the central nervous system. For years it was debated whether it should be activated or blocked for metabolic purposes; the practical answer came with tirzepatide, a dual GIP/GLP-1 agonist that showed better results than GLP-1 agonism alone in its clinical trials.
Retatrutide adds the glucagon receptor to that combination. Other programmes have explored the opposite strategy (GLP-1 agonism with GIP antagonism), which shows that the biology of this receptor remains an active area of research.
The main difference between semaglutide and tirzepatide is GIP. Understanding what this receptor adds is understanding why one is compared with the other.
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Learn it in depth at the Peptide University
- Metabolic and repair (1–5) · Module 14
- Incretin physiology · Module 3
- Pharmacology of agonists: single, dual and triple · Module 3
- Evidence and comparison · Module 3
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