Dual GIP/GLP-1 Receptor Agonist / Twincretin
Tirzepatide Research Compound — Dual GIP/GLP-1 Receptor Agonist
Tirzepatide (LY3298176) is a 39-amino acid synthetic peptide that functions as a dual agonist of both the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R) — a pharmacological profile designated a 'twincretin.' It was developed by Eli Lilly as the first approved dual incretin receptor agonist and is used in metabolic research to study combined GIPR/GLP-1R axis activation.
Compound identity
- Name
- Tirzepatide
- Class
- Dual GIP/GLP-1 Receptor Agonist / Twincretin
- CAS number
- 2023788-19-2
- Molecular formula
- C₂₂₅H₃₄₈N₄₈O₆₈
- Also known as
- GIP/GLP-1 dual agonist, LY3298176, twincretin research peptide
- Sequence
- 39-aa dual GIP/GLP-1R agonist; GIP agonist scaffold (positions 1-15) + modified amino acids; C20 fatty diacid conjugated via linker to Lys20 (albumin binding); MW 4813.47 Da
Research context
Tirzepatide (CAS 2023788-19-2, MW 4813.47 Da, C₂₂₅H₃₄₈N₄₈O₆₈) is a 39-amino acid peptide built on a modified GIP(1-15) agonist scaffold with additional structural elements that confer GLP-1R co-agonism. The compound incorporates multiple non-natural amino acids including Aib substitutions at several positions for DPP-4 resistance, and a C20 fatty diacid conjugated via a γGlu-miniPEG linker to Lys20 for albumin binding — extending the half-life to approximately 5 days in humans. Unlike GLP-1R monoagonists (semaglutide, liraglutide), tirzepatide achieves balanced agonism at both GIPR and GLP-1R. GIP (glucose-dependent insulinotropic polypeptide) is the other major incretin hormone, secreted from intestinal K cells in response to fat and carbohydrate ingestion; it potentiates insulin secretion and has additional roles in adipose tissue lipid storage, bone metabolism, and CNS energy balance signaling.
The research rationale for dual GIPR/GLP-1R agonism emerged from rodent genetics: GIPR-knockout animals show an altered metabolic phenotype on a high-fat diet, and GIPR modulation combined with GLP-1R agonism produced additive effects in rodent models. The GIPR/GLP-1R co-agonism approach in tirzepatide was designed to engage two complementary receptor axes: GLP-1R agonism acts on gastric motility and central energy-balance circuits, while GIPR agonism in adipose tissue (GIPR is expressed on adipocytes) is studied for effects on lipid handling and GLP-1R sensitization. Research using tirzepatide as a dual receptor probe has examined GIPR/GLP-1R synergy in β-cell insulin secretion, adipocyte biology, and hepatic lipid metabolism.
As a research reagent, tirzepatide is used in studies of dual incretin receptor pharmacology, GIPR and GLP-1R cross-talk, adipocyte lipid metabolism, and β-cell function. Research-grade tirzepatide is typically supplied as a lyophilized compound, with per-batch Certificate of Analysis confirming identity by mass spectrometry and purity ≥99% by HPLC.
Frequently asked questions
What is tirzepatide?+
Tirzepatide (CAS 2023788-19-2, LY3298176) is a 39-amino acid dual agonist of the GIP receptor (GIPR) and GLP-1 receptor (GLP-1R). Its 'twincretin' profile — engaging both major incretin receptors — distinguishes it from GLP-1R monoagonists such as semaglutide. As a research compound, tirzepatide is used to probe dual GIPR/GLP-1R signaling, adipocyte biology, and β-cell function.
How does tirzepatide differ from semaglutide?+
Semaglutide is a GLP-1R monoagonist (acts only at GLP-1R). Tirzepatide is a dual GIPR/GLP-1R agonist — it activates both the GIP receptor and the GLP-1 receptor. GIPR is expressed on β-cells (potentiates insulin secretion), adipocytes (lipid metabolism), bone cells, and CNS neurons. The additional GIPR agonism gives tirzepatide a distinct receptor-pharmacology profile, which is the property research uses it for.
What is the GIPR (GIP receptor) and why does dual agonism matter in research?+
GIP (glucose-dependent insulinotropic polypeptide, also called gastric inhibitory polypeptide) is a 42-aa incretin hormone secreted from intestinal K cells in response to nutrient ingestion. GIPR, the GIP receptor, is expressed on pancreatic β-cells, adipocytes, osteoblasts, and CNS neurons. Like GLP-1R, GIPR is a class B GPCR signaling primarily through cAMP. Dual GIPR/GLP-1R agonism is studied in research because it provides a tool to examine whether incretin receptor co-activation synergizes, is additive, or involves cross-sensitization — questions relevant to understanding metabolic disease biology and therapeutic mechanism.
Is tirzepatide a research-only compound?+
Yes. Tirzepatide is classified as a research compound for in-vitro and pre-clinical laboratory research use only — not for human consumption. Pharmaceutical-grade drug products containing this molecule require a valid prescription and are dispensed through licensed pharmacies; research-grade tirzepatide is a laboratory reagent and is not a substitute for one.
Research use only
All products are intended for laboratory and research use only (RUO) and are not for human consumption, ingestion, or any in-vivo use.
The statements on this page have not been evaluated by the FDA. Tirzepatide is not intended to diagnose, treat, cure, or prevent any disease. Content is provided for laboratory research reference only.