GLP2-T
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These products are for laboratory research only and not intended for medical use. They are not FDA-approved to diagnose, treat, cure, or prevent any disease. By purchasing, you certify they will be used solely for research and not for human or animal consumption.
Research Summary
8 PubMed CitationsOverview Tirzepatide (LY3298176) is a 39-amino-acid synthetic peptide engineered as a dual agonist of the GIP and GLP-1 receptors - the two principal incretin receptors. The peptide backbone is derived from the native GIP sequence and includes two 2-aminoisobutyric acid (Aib) residues that confer resistance to DPP-IV degradation, together with a C20 fatty-diacid chain attached at Lys20 that promotes reversible albumin binding and a circulating half-life of roughly five days.[1][4] Native GIP and GLP-1 are incretin hormones released from intestinal K-cells and L-cells respectively in response to nutrient intake, and both potentiate glucose-dependent insulin secretion from pancreatic beta-cells. Tirzepatide is studied as a single molecule that engages both pathways simultaneously, allowing investigators to probe the combined and interacting effects of GIP-receptor and GLP-1-receptor signaling on insulin secretion, glucagon dynamics, and energy-balance endpoints.[2][7] Discovery and design rationale Tirzepatide was reported by Coskun and colleagues at Eli Lilly as the first unimolecular...
GLP2-T — Research Data at a Glance
| Property | Value |
|---|---|
| Molecular Formula | C225H348N48O68 |
| Molecular Weight | 4813.5 Da |
| CAS Number | 2023788-19-2 |
| Amino Acid Sequence | Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Aib-Leu-Asp-Lys-Ile-Ala-Gln-L... |
| PubMed Citations Referenced | 8 |
| Contributing Researchers | 2 |
| Storage Conditions | Store lyophilized at 2-8C (refrigerated). |
| Purity Standard | ≥99% (HPLC verified, 3rd-party COA) |
| Research Use Only | Not for human consumption. RUO only. |
Overview
Overview
Tirzepatide (LY3298176) is a 39-amino-acid synthetic peptide engineered as a dual agonist of the GIP and GLP-1 receptors - the two principal incretin receptors. The peptide backbone is derived from the native GIP sequence and includes two 2-aminoisobutyric acid (Aib) residues that confer resistance to DPP-IV degradation, together with a C20 fatty-diacid chain attached at Lys20 that promotes reversible albumin binding and a circulating half-life of roughly five days.[1][4]
Native GIP and GLP-1 are incretin hormones released from intestinal K-cells and L-cells respectively in response to nutrient intake, and both potentiate glucose-dependent insulin secretion from pancreatic beta-cells. Tirzepatide is studied as a single molecule that engages both pathways simultaneously, allowing investigators to probe the combined and interacting effects of GIP-receptor and GLP-1-receptor signaling on insulin secretion, glucagon dynamics, and energy-balance endpoints.[2][7]
Discovery and design rationale
Tirzepatide was reported by Coskun and colleagues at Eli Lilly as the first unimolecular dual GIP/GLP-1 receptor agonist to reach clinical proof of concept. The design objective was to combine GIP-receptor and GLP-1-receptor agonism in a single fatty-acylated peptide, testing the hypothesis that balanced co-agonism produces greater metabolic effects than GLP-1-receptor agonism alone.[1]
Research framework
Within the incretin research-peptide family, tirzepatide is most directly compared with selective GLP-1-receptor agonists such as semaglutide and with the triple GIP/GLP-1/glucagon agonist retatrutide. Tirzepatide is the dual-agonist reference compound in this set, giving investigators a tool to isolate the contribution of added GIP-receptor engagement relative to GLP-1-only agonism.[5][6]
Mechanism of Action
Mechanism of Action
Dual Incretin Receptor Agonism
Tirzepatide is a full agonist at both the GIP receptor and the GLP-1 receptor - class B (secretin-family) Gs-coupled GPCRs expressed on pancreatic beta-cells and alpha-cells, adipocytes, and central-nervous-system neurons involved in appetite regulation. Receptor occupancy elevates intracellular cAMP and activates PKA signaling, which in the beta-cell potentiates glucose-dependent insulin secretion.[4][2]
Imbalanced / Biased Agonism
Pharmacology studies describe tirzepatide as an imbalanced dual agonist: it behaves much like native GIP at the GIP receptor, but shows biased agonism at the GLP-1 receptor, with comparatively weaker beta-arrestin recruitment relative to cAMP signaling. This distinctive signaling profile is an active area of research into how co-agonism differs mechanistically from single GLP-1-receptor agonism.[4]
DPP-IV Resistance and Pharmacokinetics
The two Aib substitutions eliminate the N-terminal DPP-IV cleavage sites, and the C20 fatty-diacid moiety drives reversible albumin binding. Together these modifications extend the circulating half-life to about five days, enabling sustained dual-receptor activation in once-weekly research dosing models.[1]
Metabolic Endpoints in Research Models
| Endpoint | Direction | Model Context |
|---|---|---|
| Glucose-dependent insulin secretion | Increased | Isolated islet and rodent glucose-tolerance models[1] |
| Glucagon (fasting) | Modulated | Clamp and mixed-meal research protocols[2] |
| Gastric emptying | Slowed | Acetaminophen-absorption and imaging models[2] |
| Food intake / body weight | Decreased | Diet-induced-obese rodent models[7] |
| Adipose insulin sensitivity | Increased | Metabolic-phenotyping research models[7] |
Receptor Selectivity
Tirzepatide engages the GIP and GLP-1 receptors with high potency and does not significantly activate the glucagon receptor, distinguishing it from triple-agonist peptides such as retatrutide.[6]
Research Applications
Research Applications
Tirzepatide is studied in preclinical and clinical research that probes dual GIP/GLP-1 receptor biology and its downstream metabolic effects. Reported research applications include:
- Dual-Incretin-Receptor Pharmacology - Used as a high-potency, DPP-IV-resistant co-agonist probe to characterize GIP-receptor and GLP-1-receptor coupling, cAMP/beta-arrestin balance, and receptor desensitization kinetics in recombinant cell-line and primary islet systems.[4]
- Glucose-Dependent Insulin Secretion - Isolated pancreatic-islet and beta-cell-line preparations are used to quantify glucose-dependent insulin release and to dissect the additive contribution of GIP-receptor engagement over GLP-1-receptor agonism alone.[1]
- Energy-Balance and Body-Weight Models - Diet-induced-obese rodent models are used to study effects on food intake, adiposity, and energy expenditure.[7]
- Comparative Incretin Research - Head-to-head research designs compare tirzepatide against selective GLP-1-receptor agonists to isolate the GIP-receptor contribution to glycemic and weight endpoints.[5]
- Glucagon and Lipid-Metabolism Profiling - Clamp and mixed-meal research protocols are used to characterize effects on glucagon dynamics, lipolysis, and lipid handling.[2]
Comparative Research Context
Within the incretin research-peptide family, investigators routinely compare tirzepatide with selective GLP-1-receptor agonists (e.g., semaglutide) and with the triple GIP/GLP-1/glucagon agonist retatrutide. Tirzepatide is the dual-agonist reference of this comparator set, isolating the effect of adding GIP-receptor engagement to GLP-1-receptor agonism.[6]
Biochemical Characteristics
| Property | Value |
|---|---|
| Formula | C225H348N48O68 |
| Molecular Weight | 4813.5 Da |
| Synonyms | Tirzepatide, LY3298176, Dual GIP/GLP-1 Receptor Agonist, GIP/GLP-1 RA |
| Cas Number | 2023788-19-2 |
| Sequence | Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Aib-Leu-Asp-Lys-Ile-Ala-Gln-Lys-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (Aib at positions 2 and 13; Lys20 conjugated to a gamma-Glu / C20 fatty-diacid moiety) |
| Pubchem Cid | 156588324 |
| Monoisotopic Mass | N/A |
| Polar Area | N/A |
| Complexity | N/A |
| X Log P | N/A |
| Heavy Atom Count | N/A |
| H Bond Donor Count | N/A |
| H Bond Acceptor Count | N/A |
| Rotatable Bond Count | N/A |
Identifiers
| Pubchem Cid | |
|---|---|
| Inchi Key | |
| Inchi | |
| Smiles Isomeric | |
| Smiles Canonical | |
| Iupac Name |
Preclinical Research Summary
Research Summary
Foundational Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Coskun et al. (2018) | Cell/rodent + phase 1 | First unimolecular dual GIP/GLP-1 receptor agonist; discovery-to-proof-of-concept characterization | [1] |
| Willard et al. (2020) | Recombinant receptor assays | Characterized tirzepatide as an imbalanced/biased dual agonist (GIP-like at GIPR; biased at GLP-1R) | [4] |
| Rosenstock et al. (2021) | SURPASS-1 (T2D) | Dose-dependent reductions in HbA1c and body weight vs placebo | [6] |
| Frias et al. (2021) | SURPASS-2 (T2D) | Greater HbA1c and body-weight reduction vs semaglutide 1 mg | [5] |
| Jastreboff et al. (2022) | SURMOUNT-1 (obesity) | Substantial dose-dependent body-weight reduction in adults with obesity | [3] |
| Samms et al. (2020) | Review / preclinical | Mechanistic framework for how GIP-receptor agonism may enhance GLP-1 efficacy | [7] |
Mechanistic Themes
- Dual incretin agonism - a single peptide engages both the GIP and GLP-1 receptors
- Imbalanced/biased signaling - GIP-like at GIPR, biased (cAMP-favoring) at GLP-1R
- Extended pharmacokinetics - Aib substitutions plus C20 fatty-diacid albumin binding support ~5-day half-life
- Glucose-dependent action - insulinotropic effect is conditioned on ambient glucose
Authors & Attribution
✍️ Article Author
Dr. Daniel J. Drucker
Daniel J. Drucker, OC, MD, FRSC, is a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Professor of Medicine at the University of Toronto. Dr. Drucker is one of the world's foremost authorities on incretin biology and the GIP and GLP-1 hormone systems that underlie dual incretin agonists such as tirzepatide, with over 800 publications and numerous awards including the Canada Gairdner International Award and the Banting Medal for Scientific Achievement. Daniel J. Drucker is being referenced as one of the leading scientists in the field of incretin (GIP/GLP-1) research relevant to Tirzepatide. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →🎓 Scientific Journal Author
Dr. Juan P. Frias
Juan P. Frias, MD, is a clinical investigator specializing in diabetes and metabolic disease and a principal investigator on multiple pivotal tirzepatide trials, including SURPASS-2, which compared tirzepatide with semaglutide in type 2 diabetes. He has authored numerous peer-reviewed publications on incretin-based therapies. Juan P. Frias is being referenced as one of the leading clinical investigators involved in the research of Tirzepatide. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →Dr. Juan P. Frias is being referenced as one of the leading scientists involved in the research and development of GLP2-T. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
Referenced Citations
Coskun 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.
PubMedMin T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021;12(1):143-157.
PubMedJastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216.
PubMedWillard FS, Douros JD, Gabe MB, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5(17):e140532.
PubMedFrias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503-515.
PubMedRosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155.
PubMedSamms RJ, Coghlan MP, Sloop KW. How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410-421.
PubMedHammoud R, Drucker DJ. Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. Nat Rev Endocrinol. 2023;19(4):201-216.
PubMedRUO Disclaimer
For Research Use Only (RUO). Not intended for human consumption, clinical use, or as a drug, food, cosmetic, or medical device. This product has not been evaluated by the FDA and is supplied solely for in-vitro laboratory research by qualified professionals.
Certificate of Analysis
Each lot is independently tested by accredited third-party laboratories (ISO 17025) at 99%+ purity.
Latest Lab Report
Storage & Handling
Summary
Store lyophilized at 2-8C (refrigerated). After reconstitution with bacteriostatic water, store refrigerated (2-8C) and use within 30 days. Do not freeze the reconstituted solution.
Lyophilized Peptide Storage
Store lyophilized tirzepatide vials at 2C to 8C (36F-46F), protected from light. For long-term storage, keep frozen at -20C. Stable for up to 24 months under recommended conditions. Do not use beyond the expiration date printed on the vial.
Reconstitution
Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and gently swirl - do not shake. Allow the powder to dissolve fully; the reconstituted solution should appear clear and colorless.
After Reconstitution
Store the reconstituted solution refrigerated at 2C to 8C and use within 30 days.
Handling Precautions
Inspect the reconstituted solution visually prior to use. Do not use if it appears cloudy, discolored, or contains particulate matter. Each vial is accompanied by a Certificate of Analysis (COA) detailing purity verification via RP-HPLC and Mass Spectrometry (MS). This product is for research use only (RUO).
“Research Summary Foundational Studies Study Model Key Findings Ref Coskun et al.”
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