Tirzepatide

About Tirzepatide

Tirzepatide (LY3298176) is a synthetic 39-amino-acid peptide belonging to a new class of dual incretin receptor agonists. It is built on the human GIP (glucose-dependent insulinotropic polypeptide) molecule and simultaneously activates two receptors — GIP and GLP-1. The molecule is modified with a fatty-acid (C20 diacid) moiety, which makes it resistant to enzymatic degradation and suitable for long-duration studies. Supplied strictly for laboratory research and not intended for human consumption.

How it works

Tirzepatide binds simultaneously to two incretin receptors — GIP and GLP-1 — and in studies displays an "imbalanced" profile: high affinity for the GIP receptor (comparable to native GIP) and roughly 18–20 times weaker affinity for the GLP-1 receptor. At the GLP-1 receptor, biased signaling is observed that favors cAMP production over β-arrestin recruitment, which in research models enhances glucose-dependent insulin secretion. Through these receptors the compound, in studies, modulates insulin and glucagon release, slows gastric emptying, and acts on the brain's satiety centers as well as on lipid and glucose metabolism in adipose tissue and the liver.

What's studied / benefits

• In the SURMOUNT-1 study, the 15 mg dose was associated with a body-weight reduction of approximately 20.9% over 72 weeks, compared with 3.1% in the placebo group
• In the SURPASS program, a reduction in glycated hemoglobin (HbA1c) of up to ~2.0–2.5% was observed — a measure of glucose control in type 2 diabetes models
• A reduction in systolic blood pressure was recorded (in the range of approximately -2.8 to -12.6 mmHg by the end of the SURPASS studies)
• Studies noted improvements in cardiometabolic markers — the lipid profile and inflammatory indicators
• An extended half-life (~5 days), thanks to reversible binding to albumin, maintains stable compound levels on a once-weekly schedule in research protocols

Research applications

• Research into the mechanisms of dual GIP/GLP-1 agonism and biased receptor signaling
• Study of glucose metabolism regulation and insulin secretion in type 2 diabetes models (the SURPASS program)
• Research into body-weight control and adipose-tissue metabolism (the SURMOUNT program)
• Study of cardiometabolic effects — blood pressure, lipids, inflammation — as well as potential in obstructive sleep apnea (the SURPASS-CVOT and SUMMIT studies are ongoing)

Of interest to: It is most often of interest to researchers in metabolism, endocrinology and pharmacology, as well as to laboratories studying incretin mechanisms, glucose control and body-weight regulation.

This information is for educational purposes only and is not medical advice. Tirzepatide is intended for laboratory research use only — not for human consumption, medical or diagnostic use.