A triple agonist is one peptide engineered to activate three receptors. In metabolic peptide research the combination is almost always GIP, GLP-1 and the glucagon receptor, built on a proglucagon-family scaffold and stabilised with Aib substitutions and a fatty-acid chain for albumin binding.
Why a third receptor
The incretin arms supply glucose-dependent insulin signalling and appetite effects; the glucagon arm adds a reported energy-expenditure and hepatic lipid-oxidation component that neither incretin provides. The engineering difficulty is that glucagon receptor activity raises hepatic glucose output, so the incretin potency must be weighted heavily enough to offset it. Getting that balance right — not adding a third receptor per se — is the technical problem.
The reference example
Retatrutide is the most studied triple agonist, with published human trial data for the investigational drug reported through phase 2 and into phase 3. Those results describe the clinical candidate under its own protocol, not research-grade material of the same sequence.
Related terms
dual agonist · incretin · research use only. Compare in Retatrutide vs Tirzepatide, or browse GLP-1 and incretin peptides.