Exenatide

Identification

Summary

Exenatide is a GLP-1 agonist used in the management of type 2 diabetes mellitus.

Brand Names
Bydureon, Byetta
Generic Name
Exenatide
DrugBank Accession Number
DB01276
Background

Exenatide is a glucagon-like peptide-1 (GLP-1) analogLabel. It functions to activate the GLP-1 receptor and increases insulin secretion, decrease glucagon secretion, and slow gastric emptying to improve glycemic controlLabel. Exenatide was given FDA approval on April 28, 20054.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Protein Structure
Db01276
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

Pharmacology

Indication

Exenatide is indicated for improving glycemic control in adults with type 2 diabetes mellitus along with diet and exerciseLabel.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

When patients take exenatide the body's natural response to glucose is modulatedLabel. More insulin and less glucagon are released in response to glucose, though in cases of hypoglycemia a normal amount of glucagon is releasedLabel. Exenatide also slows gastric emptying, leading to a slower and prolonged release of glucose into the systemic circulationLabel. Together these effects prevent hyper and hypoglycemiaLabel.

Mechanism of action

Exenatide is a human glucacon-like peptide-1(GLP-1) receptor agonistLabel. By activating this receptor, insulin secretion is increased and glucagon secretion is decreased in a glucose dependant mannerLabel. Exenatide also slows gastric emptying and decreases food intakeLabel. These effects work synergistically to improve glycemic control by reducing the likelihood of hyper and hypoglycemiaLabel.

TargetActionsOrganism
AGlucagon-like peptide 1 receptor
agonist
Humans
Absorption

Exenatide reaches a peak plasma concentration in 2.1 hoursLabel. Because exenatide is administerd subcutaneously, the bioavailability is 11.

Volume of distribution

28.3LLabel.

Protein binding

Protein binding of exenatide has not been determined5.

Metabolism

Exenatide is filtered through the glomerulus before being degraded to smaller peptides and amino acids by dipeptidyl peptidase-4, metalloproteases, endopeptidase 24-11, amino proteases, and serine proteasesLabel,3. It is currently believed that the metalloproteases are responsible for most of the degradation of exenatide3. Exenatide is metabolised to small peptides <3 amino acids in length by enzymes in the kidney2.

Route of elimination

Exenatide is mainly eliminated by glomerular filtration followed by proteolysis before finally being eliminated in the urineLabel,2.

Half-life

2.4 hoursLabel

Clearance

9.1 L/hourLabel.

Adverse Effects
Adverseeffects
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Toxicity

In animal studies, exenatide was associated with fetal deformities of ribs and vertebrae as well as slowed growthLabel. In humans, uncontrolled hyperglycemia can be associated with an up to 25% risk of miscarriageLabel. No human studies in pregnancy have been performed with exenatide and so exenatide should only be prescribed in pregnancy if the benefit to the mother and fetus outweigh the risksLabel. In mice, exenatide is excreted in the milk at a concentration 2.5% of the plasma concentration though this data may not be applicable to humansLabel. The effect of exenatide on breastfed infants is also unknown and so the risk and benefit of breastfeeding while taking exenatide must be weighedLabel. There is no data for the use of exenatide in pediatric patientsLabel. Geriatric patients do not have different results for safety and efficacy of exenatide though caution should still be used in this group as they are at higher risk of renal impairment or other comorbidities that may affect the liklihood of adverse effectsLabel. No dosage adjustments are necessary for patients with creatinine clearance ≥50mL/min, though prescribing to patients with creatinine clearance 30-50mL/min should be done cautiouslyLabel. Exenatide is not recommended for patients with creatinine clearance <30mL/minLabel. Hepatic impairment is not expected to affect clearance of exenatide though no studies have been performed to confirm thisLabel.

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.
DrugInteraction
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Exenatide.
AcebutololThe therapeutic efficacy of Exenatide can be increased when used in combination with Acebutolol.
AcenocoumarolExenatide can cause an increase in the absorption of Acenocoumarol resulting in an increased serum concentration and potentially a worsening of adverse effects.
AcetazolamideThe therapeutic efficacy of Exenatide can be increased when used in combination with Acetazolamide.
AcetohexamideExenatide may increase the hypoglycemic activities of Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Exenatide can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidThe risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Exenatide.
AlbiglutideThe risk or severity of hypoglycemia can be increased when Exenatide is combined with Albiglutide.
AlclometasoneThe risk or severity of hyperglycemia can be increased when Alclometasone is combined with Exenatide.
AlogliptinThe risk or severity of hypoglycemia can be increased when Exenatide is combined with Alogliptin.
Interactions
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Food Interactions
  • Take before a meal. Inject subcutaneously within 60 minutes before morning and evening meals.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BydureonInjection, powder, for suspension, extended release2 mgSubcutaneousAstra Zeneca Ab2016-09-08Not applicableEU flag
BydureonKit2 mg/0.65mLSubcutaneousAmylin Pharmaceuticals, Llc.2012-01-272018-01-31US flag
Bydureon2 mg/0.65mLSubcutaneousAstraZeneca Pharmaceuticals LP2015-02-012020-11-30US flag
BydureonInjection, powder, for suspension, extended release2 mgSubcutaneousAstra Zeneca Ab2016-09-08Not applicableEU flag
BydureonInjection, powder, for suspension, extended release2 mgSubcutaneousAstra Zeneca Ab2016-09-08Not applicableEU flag
BydureonInjection, powder, for suspension, extended release; Kit2 mg / doseSubcutaneousAstra Zeneca2016-02-16Not applicableCanada flag
BydureonInjection2 mgSubcutaneousAstra Zeneca Ab2020-12-21Not applicableEU flag
BydureonInjection, suspension, extended release2 mg/0.65mLSubcutaneousAstraZeneca Pharmaceuticals LP2014-09-08Not applicableUS flag
BydureonInjection, powder, for suspension, extended release2 mgSubcutaneousAstra Zeneca Ab2016-09-08Not applicableEU flag
BydureonKit2 mg/0.65mLSubcutaneousAmylin Pharmaceuticals, Llc.2012-01-272018-01-31US flag

Categories

ATC Codes
A10BJ01 — Exenatide
Drug Categories
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
  • Humans and other mammals

Chemical Identifiers

UNII
9P1872D4OL
CAS number
141758-74-9

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. Gao W, Jusko WJ: Target-mediated pharmacokinetic and pharmacodynamic model of exendin-4 in rats, monkeys, and humans. Drug Metab Dispos. 2012 May;40(5):990-7. doi: 10.1124/dmd.111.042291. Epub 2012 Feb 15. [Article]
  2. Copley K, McCowen K, Hiles R, Nielsen LL, Young A, Parkes DG: Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab. 2006 May;7(4):367-74. [Article]
  3. Liao S, Liang Y, Zhang Z, Li J, Wang J, Wang X, Dou G, Zhang Z, Liu K: In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805. doi: 10.1371/journal.pone.0116805. eCollection 2015. [Article]
  4. FDA Drug Approval Package: Exenatide [Link]
  5. FDA Pharmacology Review: Exenatide [Link]
KEGG Drug
D04121
PubChem Substance
46509017
RxNav
60548
ChEMBL
CHEMBL414357
Therapeutic Targets Database
DAP001038
PharmGKB
PA164749238
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Exenatide
FDA label
Download (1.34 MB)
MSDS
Download (22.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentDiabetes1
4CompletedBasic ScienceDiabetes / Impaired Glucose Tolerance1
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedDiagnosticHealthy Subjects (HS)1
4CompletedPreventionDiabetic Nephropathy1
4CompletedTreatmentAcute Coronary Syndrome (ACS) / Hyperglycemia / Myocardial Infarction1
4CompletedTreatmentCongestive Heart Failure (CHF) / Type 2 Diabetes Mellitus1
4CompletedTreatmentDisorder of Glucose Regulation / Overweight and Obesity / Polycystic Ovarian Syndrome (PCOS)1
4CompletedTreatmentFatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD1
4CompletedTreatmentFatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD / Type 2 Diabetes Mellitus2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amylin Pharmaceuticals
  • Baxter International Inc.
  • CP Pharmaceuticals Ltd.
  • Eli Lilly & Co.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
InjectionSubcutaneous2 mg
Injection, powder, for suspension, extended releaseSubcutaneous2 MG
Injection, powder, for suspension, extended release; kitSubcutaneous2 mg / dose
Injection, suspensionParenteral; Subcutaneous2 MG
Injection, suspensionSubcutaneous2 MG
Injection, suspension, extended releaseSubcutaneous2 mg/0.65mL
KitSubcutaneous2 mg/0.65mL
PowderSubcutaneous
Injection, suspension, extended releaseSubcutaneous2 mg/0.85mL
Suspension, extended releaseSubcutaneous2 mg / dose
Injection, powder, for suspensionSubcutaneous2 mg
InjectionSubcutaneous
InjectionSubcutaneous250 ug/1mL
Injection, solutionParenteral; Subcutaneous10 MICROGRAMMI
Injection, solutionParenteral; Subcutaneous5 MICROGRAMMI
Injection, solutionSubcutaneous10 micrograms
Injection, solutionSubcutaneous5 micrograms
SolutionSubcutaneous10 mcg / act
SolutionSubcutaneous5 mcg / act
SolutionSubcutaneous
Injection, powder, for solution
SolutionSubcutaneous250 mcg
Powder1 g/1g
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)Region
US8216180Yes2012-07-102028-07-12US flag
US8439864Yes2013-05-142028-09-25US flag
US6667061Yes2003-12-232020-11-25US flag
US6495164No2002-12-172020-05-25US flag
US5424286No1995-06-132016-12-01US flag
US6858576No2005-02-222017-01-06US flag
US6872700No2005-03-292020-01-14US flag
US6956026No2005-10-182018-01-07US flag
US7741269No2010-06-222018-01-07US flag
US7297761No2007-11-202017-10-15US flag
US7521423No2009-04-212017-10-15US flag
US6902744No2005-06-072020-01-14US flag
US9238076Yes2016-01-192024-10-15US flag
US8906851Yes2014-12-092027-02-18US flag
US7612176Yes2009-11-032025-10-13US flag
US8431685Yes2013-04-302025-10-13US flag
US8461105Yes2013-06-112025-10-13US flag
US8329648Yes2012-12-112027-02-18US flag
US7456254Yes2008-11-252025-12-30US flag
US7563871Yes2009-07-212024-10-15US flag
US6824822Yes2004-11-302023-04-09US flag
US6479065No2002-11-122020-08-10US flag
US7223440Yes2007-05-292022-03-03US flag
US8685934No2014-04-012030-05-26US flag
US8501698Yes2013-08-062027-12-20US flag
US6414126No2002-07-022020-10-04US flag
US6515117Yes2003-02-042026-04-04US flag
US6936590No2005-08-302020-10-04US flag
US9198925No2015-12-012020-10-04US flag
US7919598No2011-04-052029-12-16US flag
US8361972Yes2013-01-292028-09-21US flag
US8716251No2014-05-062028-03-21US flag
US7851502No2010-12-142028-08-19US flag
US8221786No2012-07-172028-03-21US flag
US9320853Yes2016-04-262028-09-25US flag
US8827963Yes2014-09-092029-08-04US flag
US8712615No2014-04-292030-01-18US flag
US8998876Yes2015-04-072030-07-07US flag
US8758292Yes2014-06-242028-05-12US flag
US8690837Yes2014-04-082029-11-19US flag
US8895033Yes2014-11-252031-04-04US flag
US8721615Yes2014-05-132030-07-18US flag
US9884092Yes2018-02-062027-02-18US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
isoelectric point4.86https://www.karger.com/Article/FullText/492409

Targets

Drugtargets2
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insights and accelerate drug research.
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Learn more
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
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Geelhoed-Duijvestijn PH: Incretins: a new treatment option for type 2 diabetes? Neth J Med. 2007 Feb;65(2):60-4. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  10. Barnett AH: Exenatide. Drugs Today (Barc). 2005 Sep;41(9):563-78. [Article]
  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. [Article]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Virus receptor activity
Specific Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by bindi...
Gene Name
DPP4
Uniprot ID
P27487
Uniprot Name
Dipeptidyl peptidase 4
Molecular Weight
88277.935 Da
References
  1. Liao S, Liang Y, Zhang Z, Li J, Wang J, Wang X, Dou G, Zhang Z, Liu K: In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805. doi: 10.1371/journal.pone.0116805. eCollection 2015. [Article]

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
  1. 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. [Article]

Drug created on May 16, 2007 20:43 / Updated on September 27, 2021 07:54