Incretin / GLP-1
FDA Approved
Tirzepatide
Also known as: LY3298176
Dual GIP and GLP-1 receptor agonist. Studied in metabolic research.
Research overview
Tirzepatide (development code LY3298176; licensed medicines) is a synthetic peptide with an attached fatty acid chain that activates the receptors for two gut hormones: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1. It was developed by Eli Lilly. In the UK and EU it is licensed as for type 2 diabetes and for weight management alongside diet and exercise. In the US is licensed for type 2 diabetes, for weight management and for moderate to severe obstructive sleep apnoea in adults with obesity. These licences rest on large randomised phase 3 trials: the SURPASS trials in type 2 diabetes and the SURMOUNT trials in obesity (Jastreboff et al., NEJM 2022).
Why adding GIP receptor activity to GLP-1 receptor activity matters is not fully understood. In animal studies, both activating and blocking the GIP receptor have been reported to add to the weight change seen with GLP-1 drugs, and these two routes appear to work through different brain areas in mice (Lewis et al., Nat Metab 2026). The research material supplied here is not the licensed medicine. Supplied for laboratory research use only.
Mechanism of action
Tirzepatide binds and activates two G-protein coupled receptors, the GIP receptor and the GLP-1 receptor. In cell studies it acts much like natural GIP at the GIP receptor and engages that receptor more than the GLP-1 receptor; at the GLP-1 receptor it favours one signalling route (cyclic AMP) over another (beta-arrestin), so the receptor is pulled into the cell less than with natural GLP-1 (Willard et al., 2020). In mice, its glucose-dependent insulin release worked through both receptors.