Identification
- Name
- Exenatide
- Accession Number
- DB01276
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Hormones - Description
Exenatide, derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern US, is a functional analog of Glucagon-Like Peptide-1 (GLP-1), a naturally occuring peptide.
- Protein structure
- Protein chemical formula
- C184H282N50O60S
- Protein average weight
- 4186.6 Da
- Sequences
>Exenatide HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS
Download FASTA Format- Synonyms
- Exenatida
- Exenatide
- Exenatide synthetic
- Exendin 4
- Exendin-4
- Synthetic exendin-4
- External IDs
- AC 2993 / AC-002993 / AC-2993 / AC-2993A / AC-2993LAR / AC002993 / AC2993 / AC2993A / DA-3091 / ITCA-650 / LY-2148568 / LY2148568
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Bydureon Injection, powder, for suspension, extended release 2 mg Subcutaneous Astra Zeneca Ab 2011-06-17 Not applicable EU Bydureon Kit 2 mg/0.65mL Amylin Pharmaceuticals, Llc. 2012-01-27 2018-01-31 US Bydureon Kit 2 mg/0.65mL AstraZeneca Pharmaceuticals LP 2015-02-01 Not applicable US Bydureon Injection, powder, for suspension, extended release 2 mg Subcutaneous Astra Zeneca Ab 2011-06-17 Not applicable EU Bydureon Injection, suspension, extended release 2 mg/0.65mL Subcutaneous AstraZeneca Pharmaceuticals LP 2014-09-08 Not applicable US Bydureon Injection, powder, for suspension, extended release 2 mg Subcutaneous Astra Zeneca Ab 2011-06-17 Not applicable EU Bydureon Injection, powder, for suspension, extended release; Kit 2 mg Subcutaneous Astra Zeneca 2016-02-16 Not applicable Canada Bydureon Injection, powder, for suspension, extended release 2 mg Subcutaneous Astra Zeneca Ab 2011-06-17 Not applicable EU Bydureon Kit 2 mg/0.65mL Amylin Pharmaceuticals, Llc. 2012-01-27 2018-01-31 US BYDUREON BCise Injection, suspension, extended release 2 mg/0.85mL Subcutaneous AstraZeneca Pharmaceuticals LP 2017-12-01 Not applicable US - International/Other Brands
- Bydureon / Byetta
- Categories
- Alimentary Tract and Metabolism
- Amino Acids, Peptides, and Proteins
- Biological Factors
- Blood Glucose Lowering Agents
- Bodily Secretions
- Complex Mixtures
- Drugs Used in Diabetes
- Fluids and Secretions
- GLP-1 Agonists
- Glucagon-Like Peptide 1
- Glucagon-like Peptide-1 (GLP-1) Agonists
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hypoglycemia-Associated Agents
- Incretin Mimetics
- Incretins
- Toxins, Biological
- Venoms
- UNII
- 9P1872D4OL
- CAS number
- 141758-74-9
Pharmacology
- Indication
Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control.
- Associated Conditions
- Pharmacodynamics
Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins.
- Mechanism of action
Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals.
Target Actions Organism AGlucagon-like peptide 1 receptor agonistHumans - Absorption
Following subcutaneous administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2.1 hours.
- Volume of distribution
- 28.3 L
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
Nonclinical studies have shown that exenatide is predominantly eliminated by glomerular filtration with subsequent proteolytic degradation.
- Half life
Mean terminal half-life is 2.4 hours.
- Clearance
- Apparent cl=9.1 L/hr
- Toxicity
Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin Exenatide can cause an increase in the absorption of (R)-warfarin resulting in an increased serum concentration and potentially a worsening of adverse effects. (S)-Warfarin Exenatide can cause an increase in the absorption of (S)-Warfarin resulting in an increased serum concentration and potentially a worsening of adverse effects. 2,4-thiazolidinedione The risk or severity of hypoglycemia can be increased when Exenatide is combined with 2,4-thiazolidinedione. 4-hydroxycoumarin Exenatide can cause an increase in the absorption of 4-hydroxycoumarin resulting in an increased serum concentration and potentially a worsening of adverse effects. 5-(2-methylpiperazine-1-sulfonyl)isoquinoline The therapeutic efficacy of Exenatide can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Exenatide. Acenocoumarol Exenatide can cause an increase in the absorption of Acenocoumarol resulting in an increased serum concentration and potentially a worsening of adverse effects. Acetazolamide The therapeutic efficacy of Exenatide can be increased when used in combination with Acetazolamide. Acetohexamide Exenatide may increase the hypoglycemic activities of Acetohexamide. Acetyl sulfisoxazole The therapeutic efficacy of Exenatide can be increased when used in combination with Acetyl sulfisoxazole. - Food Interactions
- Not Available
References
- Synthesis Reference
Matthieu Giraud, Anne-Sophie Droz, Stephane Varray, El Djouhar Rekai, Marie-Helene Brichard, Daniel Latassa, Christine Devijver, Pascal Gilles, Jeanne-Marie Cauvin, Fernando Albericio, Marta Paradis Bas, "PROCESS FOR THE PRODUCTION OF EXENATIDE AND OF AN EXENATIDE ANALOGUE." U.S. Patent US20110046349, issued February 24, 2011.
US20110046349- General References
- Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG: Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005 Oct 18;143(8):559-69. [PubMed:16230722]
- External Links
- KEGG Drug
- D04121
- PubChem Substance
- 46509017
- ChEMBL
- CHEMBL414357
- Therapeutic Targets Database
- DAP001038
- PharmGKB
- PA164749238
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Exenatide
- ATC Codes
- A10BX04 — Exenatide
- AHFS Codes
- 68:20.06 — Incretin Mimetics
- FDA label
- Download (683 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Amylin Pharmaceuticals
- Baxter International Inc.
- CP Pharmaceuticals Ltd.
- Eli Lilly & Co.
- Physicians Total Care Inc.
- Dosage forms
Form Route Strength Injection, powder, for suspension, extended release Subcutaneous 2 mg Injection, powder, for suspension, extended release; kit Subcutaneous 2 mg Injection, suspension, extended release Subcutaneous 2 mg/0.65mL Kit 2 mg/0.65mL Injection, suspension, extended release Subcutaneous 2 mg/0.85mL Injection Subcutaneous 250 ug/1mL Injection, solution Subcutaneous 10 micrograms Injection, solution Subcutaneous 5 micrograms Solution Subcutaneous 250 mcg - Prices
Unit description Cost Unit Byetta 10 MCG Pen 10 mcg/0.04ml Solution 2.4ml Pen 324.23USD pen Byetta 5 mcg dose pen inj 316.76USD ml Byetta 5 MCG Pen 5 mcg/0.02ml Solution 1.2ml Pen 276.57USD pen DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) US8216180 No 2012-07-10 2028-01-12 US US8439864 No 2013-05-14 2028-03-25 US US6667061 Yes 2003-12-23 2020-11-25 US US6495164 No 2002-12-17 2020-05-25 US US5424286 No 1995-06-13 2016-12-01 US US6858576 No 2005-02-22 2017-01-06 US US6872700 No 2005-03-29 2020-01-14 US US6956026 No 2005-10-18 2018-01-07 US US7741269 No 2010-06-22 2018-01-07 US US7297761 No 2007-11-20 2017-10-15 US US7521423 No 2009-04-21 2017-10-15 US US6902744 No 2005-06-07 2020-01-14 US US9238076 No 2016-01-19 2024-04-15 US US8906851 No 2014-12-09 2026-08-18 US US7612176 No 2009-11-03 2025-04-13 US US8431685 No 2013-04-30 2025-04-13 US US8461105 No 2013-06-11 2025-04-13 US US8329648 No 2012-12-11 2026-08-18 US US7456254 No 2008-11-25 2025-06-30 US US7563871 No 2009-07-21 2024-04-15 US US6824822 No 2004-11-30 2022-10-09 US US6479065 No 2002-11-12 2020-08-10 US US7223440 No 2007-05-29 2021-08-31 US US8685934 No 2014-04-01 2030-05-26 US US8501698 No 2013-08-06 2027-06-20 US US6414126 No 2002-07-02 2020-10-04 US US6515117 No 2003-02-04 2020-10-04 US US6936590 No 2005-08-30 2020-10-04 US US9198925 No 2015-12-01 2020-10-04 US US7919598 No 2011-04-05 2029-12-16 US US8361972 No 2013-01-29 2028-03-21 US US8716251 No 2014-05-06 2028-03-21 US US7851502 No 2010-12-14 2028-08-19 US US8221786 No 2012-07-17 2028-03-21 US US9320853 No 2016-04-26 2028-03-25 US US8827963 No 2014-09-09 2029-02-04 US US8712615 No 2014-04-29 2030-01-18 US US8998876 No 2015-04-07 2030-01-07 US US8758292 No 2014-06-24 2027-11-12 US US8690837 No 2014-04-08 2029-05-19 US US8895033 No 2014-11-25 2030-10-04 US US8721615 No 2014-05-13 2030-01-18 US US9884092 No 2018-02-06 2026-08-18 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
Taxonomy
- 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
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
- Briones M, Bajaj M: Exenatide: a GLP-1 receptor agonist as novel therapy for Type 2 diabetes mellitus. Expert Opin Pharmacother. 2006 Jun;7(8):1055-64. [PubMed:16722815]
- Hargrove DM, Kendall ES, Reynolds JM, Lwin AN, Herich JP, Smith PA, Gedulin BR, Flanagan SD, Jodka CM, Hoyt JA, McCowen KM, Parkes DG, Anderson CM: Biological activity of AC3174, a peptide analog of exendin-4. Regul Pept. 2007 Jun 7;141(1-3):113-9. Epub 2007 Jan 11. [PubMed:17292977]
- Wajchenberg BL: beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev. 2007 Apr;28(2):187-218. Epub 2007 Mar 12. [PubMed:17353295]
- Mack CM, Moore CX, Jodka CM, Bhavsar S, Wilson JK, Hoyt JA, Roan JL, Vu C, Laugero KD, Parkes DG, Young AA: Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures. Int J Obes (Lond). 2006 Sep;30(9):1332-40. Epub 2006 Mar 14. [PubMed:16534527]
- Geelhoed-Duijvestijn PH: Incretins: a new treatment option for type 2 diabetes? Neth J Med. 2007 Feb;65(2):60-4. [PubMed:17379930]
- Mann RJ, Nasr NE, Sinfield JK, Paci E, Donnelly D: The major determinant of exendin-4/glucagon-like peptide 1 differential affinity at the rat glucagon-like peptide 1 receptor N-terminal domain is a hydrogen bond from SER-32 of exendin-4. Br J Pharmacol. 2010 Aug;160(8):1973-84. doi: 10.1111/j.1476-5381.2010.00834.x. [PubMed:20649595]
- Degn KB, Brock B, Juhl CB, Djurhuus CB, Grubert J, Kim D, Han J, Taylor K, Fineman M, Schmitz O: Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes. 2004 Sep;53(9):2397-403. [PubMed:15331551]
- Diamant M, Bunck MC, Heine RJ: [Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2]. Ned Tijdschr Geneeskd. 2004 Sep 25;148(39):1912-7. [PubMed:15495988]
- Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman MS, Baron AD: Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm. 2005 Jan 15;62(2):173-81. [PubMed:15700891]
- Barnett AH: Exenatide. Drugs Today (Barc). 2005 Sep;41(9):563-78. [PubMed:16341288]
- Lebovitz HE: Therapeutic options in development for management of diabetes: pharmacologic agents and new technologies. Endocr Pract. 2006 Jan-Feb;12 Suppl 1:142-7. [PubMed:16627399]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Chae SY, Jin CH, Shin JH, Son S, Kim TH, Lee S, Youn YS, Byun Y, Lee MS, Lee KC: Biochemical, pharmaceutical and therapeutic properties of long-acting lithocholic acid derivatized exendin-4 analogs. J Control Release. 2010 Mar 3;142(2):206-13. doi: 10.1016/j.jconrel.2009.10.025. Epub 2009 Nov 10. [PubMed:19900495]
Drug created on May 16, 2007 14:43 / Updated on February 16, 2019 03:22