Identification
- Summary
Tirzepatide is a dual GIP and GLP-1 receptor agonist used for the treatment of type II diabetes in adults as an adjunct to diet and exercise.
- Brand Names
- Mounjaro, Zepbound
- Generic Name
- Tirzepatide
- DrugBank Accession Number
- DB15171
- Background
Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Dual GIP/GLP-1 agonists gained increasing attention as new therapeutic agents for glycemic and weight control as they demonstrated better glucose control and weight loss compared to selective GLP-1 receptor agonists in preclinical and clinical trials.1
Tirzepatide comprises a 39 amino acid linear synthetic peptide conjugated to a C20 fatty diacid moiety.1 Its protein sequence was based on the sequence of endogenous GIP, and its pharmacological action on GLP-1 receptors is comparable to endogenous GIP; however, the long half-life of tirzepatide allows for once-weekly dosing.2 Tirzepatide was approved by the FDA on May 13, 2022, under the brand name MOUNJARO by the FDA for the treatment of adults with type 2 diabetes, making it the first and only GIP and GLP-1 receptor agonist for this indication.5 Later, it was approved under a different brand name ZEPBOUND on November 8, 2023, for the chronic weight management in adults with obesity or overweight with at least one weight-related condition.9 On September 15, 2022, tirzepatide was also approved by the European Commission.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Peptides - Protein Chemical Formula
- C225H348N48O68
- Protein Average Weight
- 4810.52 Da
- Sequences
>Tirzepatide protein sequence YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS
Download FASTA FormatReferences:
- KEGG DRUG: Tirzepatide [Link]
- Synonyms
- Tirzepatide
- External IDs
- LY3298176
Pharmacology
- Indication
Tirzepatide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus or for the chronic weight management for adult patients that are obese or overweight with at least one weight-related comorbid condition such as hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea, or cardiovascular disease). 4,6,8 In Europe, it may be used as monotherapy or in combination with other drugs used to treat diabetes.6
This drug has not been studied in patients with a history of pancreatitis. Tirzepatide is not indicated for use in patients with type 1 diabetes mellitus.4
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- Associated Therapies
- Contraindications & Blackbox Warnings
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Tirzepatide is a synthetic peptide with glucose-lowering effects. It works to stimulate first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner.1,4 Tirzepatide was also shown to delay gastric emptying, lower fasting and postprandial glucose concentration, decrease food intake,4 and reduce body weight in patients with type 2 diabetes.2 Tirzepatide can increase insulin sensitivity.4
As the peptide is conjugated to a C20 fatty diacid moiety through a hydrophilic linker at the lysine residue at position 20, the drug is highly bound to albumin in the plasma, which prolongs its half-life.2
- Mechanism of action
Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) are expressed throughout the body, including pancreatic beta-cells and the gastrointestinal tract. They have been implicated in the pathophysiology of type II diabetes mellitus as GLP-1R signalling is involved in glucose control by enhancing glucose-stimulated insulin secretion, delaying gastric transit, decreasing plasma glucagon levels, and reducing body weight by activating anorexigenic pathways in the brain.1 Both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are peptide hormones involved in glucose homeostasis: they promote glucose-stimulated insulin secretion from the pancreatic beta-cells.2 However, GIP is the main incretin hormone that exerts insulinotropic effects in response to food intake.1,2
The exact mechanism of action of tirzepatide has not been fully elucidated; however, dual agonism at GIP and GLP-1R may contribute to the glycemic and weight control effects of the drug.2 Studies demonstrated that co-administration of GIP and a GLP-1R agonist more significantly increased insulin response and suppressed glucagon secretion compared to separate administration of either hormone alone.3 Tirzepatide binds to GIP and GLP-1R with high affinity.1,2 In vitro, tirzepatide has a comparable GIP receptor binding affinity to native GIP and five times lower GLP-1R affinity than that of native GLP-1.3 Tirzepatide potently activates the GLP-1R signalling pathway to stimulate glucose-dependent insulin secretion through activity at the GIP receptor (GIPR) or the GLP-1R.1 However, the role of GIPR agonism in the drug's mechanism of action requires further investigation, as the evidence of GIPR agonism on glycemic and weight control in preclinical and clinical studies are conflicting.2
Target Actions Organism AGlucagon-like peptide 1 receptor agonistHumans AGastric inhibitory polypeptide agonistHumans - Absorption
Over the dose range of 1-5 mg, the Cmax of tirzepatide ranged from 108 to 397 ng/mL.1 The mean absolute bioavailability of tirzepatide following subcutaneous administration is 80%. Following subcutaneous administration, the Tmax ranged from eight to 72 hours. The steady-state plasma concentrations were achieved following four weeks of once-weekly subcutaneous administration.4
As tirzepatide delays gastric emptying, it has the potential to affect the absorption of concomitantly administered oral medications. The US prescribing information recommends the use of caution when co-administering tirzepatide with other oral medications.4
- Volume of distribution
Following subcutaneous administration, the mean steady-state volume of distribution was 9.5 L.1 The mean apparent steady-state volume of distribution of tirzepatide following subcutaneous administration in patients with type 2 diabetes mellitus was approximately 10.3 L.4
- Protein binding
- Metabolism
Tirzepatide is metabolized by proteolytic cleavage of the peptide backbone, beta-oxidation of the C20 fatty diacid moiety, and amide hydrolysis.4
- Route of elimination
Tirzepatide is primarily excreted via urine and feces, mostly in the form of metabolites. Unchanged parent drug was not detectable in urine and feces.4
- Half-life
- Clearance
The apparent population mean clearance of tirzepatide is 0.061 L/h.4 The mean steady-state apparent clearance of tirzepatide was 0.056 L/h.1
- Adverse Effects
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There is limited information regarding the LD50 and overdose of tirzepatide. In case of an overdosage, appropriate supportive treatment should be initiated with a sufficient amount of time for observation and treatment, as tirzepatide has a long half-life.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Tirzepatide. Acebutolol The therapeutic efficacy of Tirzepatide can be increased when used in combination with Acebutolol. Acetazolamide The therapeutic efficacy of Tirzepatide can be increased when used in combination with Acetazolamide. Acetohexamide The risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Tirzepatide. Acetyl sulfisoxazole The therapeutic efficacy of Tirzepatide can be increased when used in combination with Acetyl sulfisoxazole. Acetylsalicylic acid The risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Tirzepatide. Albiglutide The risk or severity of hypoglycemia can be increased when Albiglutide is combined with Tirzepatide. Alclometasone The risk or severity of hyperglycemia can be increased when Alclometasone is combined with Tirzepatide. Alogliptin The risk or severity of hypoglycemia can be increased when Alogliptin is combined with Tirzepatide. Amcinonide The risk or severity of hyperglycemia can be increased when Amcinonide is combined with Tirzepatide. 
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- Take with or without food. Food has no clinically significant effects on drug exposure.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mounjaro Injection, solution 12.5 mg Subcutaneous Eli Lilly Nederland B.V. 2023-02-08 Not applicable EU 
Mounjaro Injection, solution 10 mg Subcutaneous Eli Lilly Nederland B.V. 2023-11-28 Not applicable EU Mounjaro Injection, solution 15 mg Subcutaneous Eli Lilly Nederland B.V. 2023-11-28 Not applicable EU Mounjaro Solution 7.5 mg / 0.5 mL Subcutaneous Eli Lilly & Co. Ltd. 2023-10-23 Not applicable Canada 
Mounjaro Injection, solution 10 mg/0.5mL Subcutaneous Eli Lilly and Company 2022-05-13 Not applicable US 
Mounjaro Injection, solution 10 mg Subcutaneous Eli Lilly Nederland B.V. 2023-11-28 Not applicable EU Mounjaro Injection, solution 2.5 mg Subcutaneous Eli Lilly Nederland B.V. 2023-02-08 Not applicable EU Mounjaro Injection, solution 2.5 mg Subcutaneous Eli Lilly Nederland B.V. 2023-11-28 Not applicable EU Mounjaro Injection, solution 2.5 mg/0.5mL Subcutaneous Eli Lilly and Company 2023-07-28 Not applicable US Mounjaro Injection, solution 10 mg Subcutaneous Eli Lilly Nederland B.V. 2023-02-08 Not applicable EU
Categories
- ATC Codes
- A10BX16 — Tirzepatide
- Drug Categories
- Alimentary Tract and Metabolism
- Amino Acids, Peptides, and Proteins
- Blood Glucose Lowering Agents
- Drugs Used in Diabetes
- Gastrointestinal Hormones
- GLP-1 Agonists
- Glucagon-Like Peptide Receptors
- Glucose-dependent Insulinotropic Polypeptide Receptor Agonist
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Incretins
- Membrane Proteins
- Nerve Tissue Proteins
- Neuropeptides
- Peptide Hormones
- Peptides
- Proteins
- Receptors, G-Protein-Coupled
- Receptors, Gastrointestinal Hormone
- Receptors, Peptide
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- OYN3CCI6QE
- CAS number
- 2023788-19-2
References
- General References
- Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A: 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 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. [Article]
- Frias JP: Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab. 2020 Nov;15(6):379-394. doi: 10.1080/17446651.2020.1830759. Epub 2020 Oct 8. [Article]
- Min 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 Jan;12(1):143-157. doi: 10.1007/s13300-020-00981-0. Epub 2020 Dec 15. [Article]
- FDA Approved Drug Products: MOUNJARO (tirzepatide) Injection, for subcutaneous use [Link]
- Eli Lilly and Company Investors News Release: FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes [Link]
- EMA Approved Drug Products: Mounjaro (tirzepatide) Subcutaneous Injection [Link]
- Pharmaceutical Technology: European Commission’s approval of Mounjaro provides hope within obesity space [Link]
- FDA Approved Drug Products: ZEPBOUND™ (tirzepatide) Injection, for subcutaneous use (November 2023) [Link]
- FDA Approves New Medication for Chronic Weight Management [Link]
- External Links
- 2601723
- Wikipedia
- Tirzepatide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Type 2 Diabetes Mellitus 1 4 Not Yet Recruiting Health Services Research Atherosclerosis / Type 2 Diabetes Mellitus 1 4 Recruiting Treatment Metabolic Diseases / Obesity 1 4 Recruiting Treatment Type 2 Diabetes Mellitus 3 3 Active Not Recruiting Treatment Heart Failure With Preserved Ejection Fraction (HFpEF) / Obesity 1 3 Active Not Recruiting Treatment Obesity / Overweight 2 3 Active Not Recruiting Treatment Obesity / Sleep Apnea 1 3 Active Not Recruiting Treatment Type 2 Diabetes Mellitus 1 3 Completed Treatment Metabolic and Nutritional Disorders / Obesity / Overweight 1 3 Completed Treatment Obesity 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 10 mg Injection, solution Subcutaneous 10 mg/0.5mL Injection, solution Subcutaneous 12.5 mg/0.5mL Injection, solution Subcutaneous 12.5 mg Injection, solution Subcutaneous 15 mg/0.5mL Injection, solution Subcutaneous 15 mg Injection, solution Subcutaneous 2.5 mg/0.5mL Injection, solution Subcutaneous 2.5 mg Injection, solution Subcutaneous 5 mg/0.5mL Injection, solution Subcutaneous 5 mg Injection, solution Subcutaneous 7.5 mg Injection, solution Subcutaneous 7.5 mg/0.5mL Solution Subcutaneous 10 mg / 0.5 mL Solution Subcutaneous 12.5 mg / 0.5 mL Solution Subcutaneous 15 mg / 0.5 mL Solution Subcutaneous 2.5 mg / 0.5 mL Solution Subcutaneous 5 mg / 0.5 mL Solution Subcutaneous 7.5 mg / 0.5 mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9474780 No 2016-10-25 2036-01-05 US US8734394 No 2014-05-27 2031-02-24 US US9402957 No 2016-08-02 2031-06-29 US US11357820 No 2019-06-14 2039-06-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <1 mg/mL https://www.selleckchem.com/msds/MSDS_P1206.pdf
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Gene Name
- GLP1R
- Uniprot ID
- P43220
- Uniprot Name
- Glucagon-like peptide 1 receptor
- Molecular Weight
- 53025.22 Da
References
- Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A: 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 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. [Article]
- FDA Approved Drug Products: MOUNJARO (tirzepatide) Injection, for subcutaneous use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion.
- Specific Function
- Gastric inhibitory polypeptide receptor binding
- Gene Name
- GIP
- Uniprot ID
- P09681
- Uniprot Name
- Gastric inhibitory polypeptide
- Molecular Weight
- 17107.37 Da
References
- Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A: 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 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. [Article]
- FDA Approved Drug Products: MOUNJARO (tirzepatide) Injection, for subcutaneous use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A: 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 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. [Article]
- Frias JP: Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab. 2020 Nov;15(6):379-394. doi: 10.1080/17446651.2020.1830759. Epub 2020 Oct 8. [Article]
- FDA Approved Drug Products: MOUNJARO (tirzepatide) Injection, for subcutaneous use [Link]
Drug created at May 20, 2019 14:55 / Updated at November 24, 2023 04:34