If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
Retatrutide-Obesity
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
What is the difference between the retatrutide and tirzepatide molecules?
Retatrutide is a novel synthetic molecule that has agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), the glucagon-like peptide-1 (GLP-1), and glucagon (GCG) receptors. Tirzepatide is a GIP and GLP-1 receptor agonist.
Retatrutide Compared With Tirzepatide
Retatrutide and tirzepatide are both incretin-based molecules administered by subcutaneous injection.1-4
Retatrutide
Retatrutide is an investigational molecule and is not currently approved in the United States.5
Retatrutide is a novel synthetic molecule, which is an agonist of the
- glucose-dependent insulinotropic polypeptide receptor (GIPR)
- glucagon-like peptide-1 receptor (GLP-1R), and
- glucagon receptor (GCGR).2
The structure of retatrutide is presented in Retatrutide Structure.
Retatrutide Receptor Activation
Retatrutide shows 8.9-fold greater potency than human GIP at the human GIPR, 2.9-fold less potency than human glucagon at the human GCGR, and 2.5-fold less potency than human GLP-1 at the human GLP-1R. In other words, retatrutide demonstrated potent agonist activity at the human GIPR and balanced activity at the human GCGR and GLP-1R.2
Retatrutide Half-Life
In a phase 1 study in healthy participants (baseline body mass index from 19 to 40 Kg/m2), the mean half-life was approximately 6 days, supporting once-weekly dosing.2
Tirzepatide
Please refer to the Enclosed Prescribing Information for approved indications of tirzepatide in the United States.
The structure of tirzepatide is presented in Tirzepatide Chemical Structure.
Tirzepatide Receptor Activation
Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1.3,4 Preclinical studies support that it binds at the GLP-1 receptor with slightly lower affinity compared to endogenous GLP-1; however, it binds at the GIP receptor with equal affinity to endogenous GIP.1,7
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018;18:3-14. https://doi.org/10.1016/j.molmet.2018.09.009
2Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247. https://doi.org/10.1016/j.cmet.2022.07.013
3Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2023.
4Zepbound [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
5Medicines in development. Eli Lilly and Company. Clinical Development Pipeline website. Accessed April 30, 2024. https://www.lilly.com/pipeline
6Data on file, Eli Lilly and Company and/or one of its subsidiaries.
7Samms RJ, Christe ME, Collins KAL, et al. GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice. J Clin Invest. 2021;131(12):e146353. https://doi.org/10.1172/JCI146353
Date of Last Review: April 19, 2024