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Identification
NameExenatide
Accession NumberDB01276
TypeBiotech
GroupsApproved, Investigational
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 structureDb01276
Related Articles
Protein chemical formulaC184H282N50O60S
Protein average weight4186.6 Da
Sequences
>Exenatide
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS
Download FASTA Format
Synonyms
AC 2993
AC-2993
AC002993
AC2993
AC2993a
Bydureon
Byetta
Exenatide
Exenatide synthetic
Synthetic exendin-4
External Identifiers
  • AC2993
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bydureonpowder for suspension, sustained-release; kit2 mgsubcutaneousAstrazeneca Canada Inc2016-02-16Not applicableCanada
Bydureoninjection, suspension, extended release2 mg/.65mLsubcutaneousAstra Zeneca Pharmaceuticals Lp2014-09-08Not applicableUs
BydureonkitAmylin Pharmaceuticals, LLC2012-01-27Not applicableUs
BydureonkitAstra Zeneca Pharmaceuticals Lp2015-02-01Not applicableUs
BydureonkitAmylin Pharmaceuticals, LLC2012-01-27Not applicableUs
Byettainjection250 ug/mLsubcutaneousAstra Zeneca Pharmaceuticals Lp2014-12-10Not applicableUs
Byettainjection250 ug/mLsubcutaneousAmylin Pharmaceuticals, LLC2005-04-28Not applicableUs
Byettainjection250 ug/mLsubcutaneousAmylin Pharmaceuticals, LLC2005-04-28Not applicableUs
Byettainjection250 ug/mLsubcutaneousPhysicians Total Care, Inc.2005-08-09Not applicableUs
Byettasolution250 mcgsubcutaneousAstrazeneca Canada Inc2011-05-31Not applicableCanada
Byettasolution250 mcgsubcutaneousAstrazeneca Canada Inc2011-06-01Not applicableCanada
Byettainjection250 ug/mLsubcutaneousAstra Zeneca Pharmaceuticals Lp2014-12-12Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII9P1872D4OL
CAS number141758-74-9
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationIndicated 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.
PharmacodynamicsExenatide 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 actionExenatide 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.
Related Articles
AbsorptionFollowing 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 bindingNot Available
MetabolismNot Available
Route of eliminationNonclinical studies have shown that exenatide is predominantly eliminated by glomerular filtration with subsequent proteolytic degradation.
Half lifeMean terminal half-life is 2.4 hours.
Clearance
  • Apparent cl=9.1 L/hr
ToxicityEffects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, suspension, extended releasesubcutaneous2 mg/.65mL
Kit
Powder for suspension, sustained-release; kitsubcutaneous2 mg
Injectionsubcutaneous250 ug/mL
Solutionsubcutaneous250 mcg
Prices
Unit descriptionCostUnit
Byetta 10 MCG Pen 10 mcg/0.04ml Solution 2.4ml Pen324.23USD pen
Byetta 5 mcg dose pen inj316.76USD ml
Byetta 5 MCG Pen 5 mcg/0.02ml Solution 1.2ml Pen276.57USD pen
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5424286 No1996-12-012016-12-01Us
US6479065 No2000-08-102020-08-10Us
US6495164 No2000-05-252020-05-25Us
US6667061 No2000-05-252020-05-25Us
US6824822 No2002-10-092022-10-09Us
US6858576 No1997-01-062017-01-06Us
US6872700 No2000-01-142020-01-14Us
US6902744 No2000-01-142020-01-14Us
US6956026 No1998-01-072018-01-07Us
US7223440 No2001-08-312021-08-31Us
US7297761 No1997-10-152017-10-15Us
US7456254 No2005-06-302025-06-30Us
US7521423 No1997-10-152017-10-15Us
US7563871 No2004-04-152024-04-15Us
US7612176 No2005-04-132025-04-13Us
US7741269 No1998-01-072018-01-07Us
US8216180 No2008-01-122028-01-12Us
US8329648 No2006-08-182026-08-18Us
US8431685 No2005-04-132025-04-13Us
US8439864 No2008-03-252028-03-25Us
US8461105 No2005-04-132025-04-13Us
US8906851 No2006-08-182026-08-18Us
US9238076 No2004-04-152024-04-15Us
Properties
StateSolid
Experimental PropertiesNot 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
  1. 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
ATC CodesA10BX04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (683 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolExenatide may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Exenatide.
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Exenatide.
ChlorpropamideExenatide may increase the hypoglycemic activities of Chlorpropamide.
DicoumarolExenatide may increase the anticoagulant activities of Dicoumarol.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Exenatide.
EtonogestrelThe serum concentration of Etonogestrel can be decreased when it is combined with Exenatide.
GliclazideExenatide may increase the hypoglycemic activities of Gliclazide.
GlimepirideExenatide may increase the hypoglycemic activities of Glimepiride.
GlipizideExenatide may increase the hypoglycemic activities of Glipizide.
GlyburideExenatide may increase the hypoglycemic activities of Glyburide.
Insulin AspartExenatide may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecExenatide may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirExenatide may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineExenatide may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineExenatide may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanExenatide may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproExenatide may increase the hypoglycemic activities of Insulin Lispro.
LeuprolideThe therapeutic efficacy of Exenatide can be decreased when used in combination with Leuprolide.
LevonorgestrelThe serum concentration of Levonorgestrel can be decreased when it is combined with Exenatide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Exenatide.
NorethisteroneThe serum concentration of Norethindrone can be decreased when it is combined with Exenatide.
OxandroloneOxandrolone may increase the hypoglycemic activities of Exenatide.
ParoxetineParoxetine may increase the hypoglycemic activities of Exenatide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Exenatide.
PhenelzinePhenelzine may increase the hypoglycemic activities of Exenatide.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Exenatide.
TestosteroneTestosterone may increase the hypoglycemic activities of Exenatide.
TolazamideExenatide may increase the hypoglycemic activities of Tolazamide.
TolbutamideExenatide may increase the hypoglycemic activities of Tolbutamide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Exenatide.
TrichlormethiazideThe therapeutic efficacy of Exenatide can be decreased when used in combination with Trichlormethiazide.
WarfarinExenatide may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
Molecular Weight:
53025.22 Da
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Geelhoed-Duijvestijn PH: Incretins: a new treatment option for type 2 diabetes? Neth J Med. 2007 Feb;65(2):60-4. [PubMed:17379930 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. Barnett AH: Exenatide. Drugs Today (Barc). 2005 Sep;41(9):563-78. [PubMed:16341288 ]
  11. 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 ]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on May 16, 2007 14:43 / Updated on July 25, 2016 02:03