Lixisenatide

Identification

Name
Lixisenatide
Accession Number
DB09265
Description

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type 2 diabetes mellitus (T2DM). It is sold under the brand name Adlyxin by Sanofi-Aventis. Adlyxin recieved FDA approval July 28, 2016 3.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 4858.56
Monoisotopic: 4855.544321891
Chemical Formula
C215H347N61O65S
Synonyms
  • des-38-proline-exendine-4 (Heloderma suspectum)-(1-39)-peptidylpenta-L-lysyl-L-lysinamide
  • DesPro38Exendin-4(1-39)-Lys6-NH2
  • Lixisenatida
  • Lixisénatide
  • Lixisenatide
External IDs
  • AQVE-10010
  • AVE 0010
  • AVE0010
  • ZP 10
  • ZP10A peptide

Pharmacology

Indication

For use as an antihyperglycemic agent in the treatment of T2DM Label.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Lixisenatide acts as an agonist at the GLP-1 receptor. In the pancreas, this agonism results in increased glucose-stimulated insulin exocytosis by beta islet cells. This produces a reduction in blood glucose due to increased glucose uptake by tissues 1. GLP-1 receptor activation in the GI tract results in delayed gastric emptying which is thought to mediate the effects of lixisenatide on postprandial blood glucose.

Mechanism of action

The activation of the GLP-1 receptor by lixisenatide results in the activation of adenylyl cyclase [19193]. This increases the concentration of cyclic adenosine monophosphate in the cell leading to the activation of protein kinase A (PKA) as well as Epac1 and Epac2. PKA, Epac1, and Epac2 are involved the in release of Ca2+ from the endoplasmic reticulum which is known as the "amplification" pathway which increases insulin release when the triggering pathway is activated. By activating this amplification pathway lixisenatide increases glucose stimulated insulin secretion.

TargetActionsOrganism
AGlucagon-like peptide 1 receptor
agonist
Humans
Absorption

tmax of 1-3.5h when administered subcutaneously Label.

Volume of distribution

100L Label

Protein binding

55% bound to plasma proteins 4.

Metabolism

Assumed to undergo proteolytic degradation Label.

Route of elimination

Assumed to be proteolytic degradation and excretion in urine Label.

Half-life

3h Label

Clearance

35L/h Label

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Thyroid C-cell adenomas occurred in rats when exposed to >15 times human exposure of 20mcg/day Label. Overdose is associated with GI side effects typical of GLP-1 receptor agonists.

Affected organisms
Not Available
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
AbacavirAbacavir may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Lixisenatide.
AcebutololThe therapeutic efficacy of Lixisenatide can be increased when used in combination with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcenocoumarolLixisenatide can cause a decrease in the absorption of Acenocoumarol resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcetaminophenAcetaminophen may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcetazolamideThe therapeutic efficacy of Lixisenatide can be increased when used in combination with Acetazolamide.
AcetohexamideLixisenatide may increase the hypoglycemic activities of Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Lixisenatide can be increased when used in combination with Acetyl sulfisoxazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Take at the same time every day.
  • Take before a meal. Take lixisenatide within one hour before the first meal of the day.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdlyxinInjection, solution100 ug/1mLSubcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUS flag
AdlyxineSolutionSubcutaneousSanofi Aventis2017-09-12Not applicableCanada flag
AdlyxineSolutionSubcutaneousSanofi Aventis2017-09-12Not applicableCanada flag
LyxumiaInjection, solution20 μgSubcutaneousSanofi Aventis Groupe2013-01-31Not applicableEU flag
LyxumiaInjection, solution20 μgSubcutaneousSanofi Aventis Groupe2013-01-31Not applicableEU flag
LyxumiaInjection, solution20 μgSubcutaneousSanofi Aventis Groupe2013-01-31Not applicableEU flag
LyxumiaInjection, solution10 μgSubcutaneousSanofi Aventis Groupe2013-01-31Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)Subcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUS flag
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)Subcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUS flag
AdlyxineLixisenatide (0.05 mg) + Lixisenatide (0.1 mg)Kit; SolutionSubcutaneousSanofi Aventis2017-09-122018-10-08Canada flag
AdlyxineLixisenatide (0.05 mg) + Lixisenatide (0.1 mg)Kit; SolutionSubcutaneousSanofi Aventis2017-09-122018-10-08Canada flag
SoliquaLixisenatide (33 mcg) + Insulin glargine (100 unit)SolutionSubcutaneousSanofi Aventis2018-09-12Not applicableCanada flag
Soliqua 100/33Lixisenatide (33 ug/1mL) + Insulin glargine (100 U/1mL)Injection, solutionSubcutaneoussanofi-aventis U.S. LLC2016-11-21Not applicableUS flag

Categories

ATC Codes
A10AE54 — Insulin glargine and lixisenatideA10BJ03 — Lixisenatide
Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
74O62BB01U
CAS number
320367-13-3
InChI Key
XVVOERDUTLJJHN-IAEQDCLQSA-N
InChI
InChI=1S/C215H347N61O65S/c1-16-115(10)173(210(337)256-141(68-74-170(299)300)194(321)261-148(94-122-98-232-126-50-24-23-49-124(122)126)199(326)258-143(89-111(2)3)196(323)247-134(58-32-40-83-223)189(316)262-149(96-160(226)285)180(307)235-100-161(286)233-104-165(290)274-85-42-60-156(274)207(334)267-154(108-280)206(333)265-151(105-277)181(308)237-101-162(287)239-117(12)213(340)276-87-44-62-158(276)214(341)275-86-43-61-157(275)208(335)268-153(107-279)204(331)249-132(56-30-38-81-221)187(314)246-131(55-29-37-80-220)186(313)245-130(54-28-36-79-219)185(312)244-129(53-27-35-78-218)184(311)243-128(52-26-34-77-217)183(310)242-127(176(227)303)51-25-33-76-216)272-201(328)146(92-120-45-19-17-20-46-120)260-197(324)144(90-112(4)5)257-190(317)135(59-41-84-231-215(228)229)255-209(336)172(114(8)9)271-177(304)116(11)240-182(309)138(65-71-167(293)294)251-192(319)139(66-72-168(295)296)252-193(320)140(67-73-169(297)298)253-195(322)142(75-88-342-15)254-191(318)137(63-69-159(225)284)250-188(315)133(57-31-39-82-222)248-203(330)152(106-278)266-198(325)145(91-113(6)7)259-200(327)150(97-171(301)302)263-205(332)155(109-281)269-212(339)175(119(14)283)273-202(329)147(93-121-47-21-18-22-48-121)264-211(338)174(118(13)282)270-164(289)103-236-179(306)136(64-70-166(291)292)241-163(288)102-234-178(305)125(224)95-123-99-230-110-238-123/h17-24,45-50,98-99,110-119,125,127-158,172-175,232,277-283H,16,25-44,51-97,100-109,216-224H2,1-15H3,(H2,225,284)(H2,226,285)(H2,227,303)(H,230,238)(H,233,286)(H,234,305)(H,235,307)(H,236,306)(H,237,308)(H,239,287)(H,240,309)(H,241,288)(H,242,310)(H,243,311)(H,244,312)(H,245,313)(H,246,314)(H,247,323)(H,248,330)(H,249,331)(H,250,315)(H,251,319)(H,252,320)(H,253,322)(H,254,318)(H,255,336)(H,256,337)(H,257,317)(H,258,326)(H,259,327)(H,260,324)(H,261,321)(H,262,316)(H,263,332)(H,264,338)(H,265,333)(H,266,325)(H,267,334)(H,268,335)(H,269,339)(H,270,289)(H,271,304)(H,272,328)(H,273,329)(H,291,292)(H,293,294)(H,295,296)(H,297,298)(H,299,300)(H,301,302)(H4,228,229,231)/t115-,116-,117-,118+,119+,125-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,156-,157-,158-,172-,173-,174-,175-/m0/s1
IUPAC Name
(4S)-4-[({[(1S,2R)-1-{[(1S)-1-{[(1S,2R)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-5-amino-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-5-amino-1-{[(1S)-1-{[({2-[(2S)-2-{[(1S)-1-{[(1S)-1-[({[(2S)-1-[(2S)-2-[(2S)-2-{[(1S)-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-carbamoylpentyl]carbamoyl}pentyl]carbamoyl}pentyl]carbamoyl}pentyl]carbamoyl}pentyl]carbamoyl}pentyl]carbamoyl}-2-hydroxyethyl]carbamoyl}pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]carbamoyl}methyl)carbamoyl]-2-hydroxyethyl]carbamoyl}-2-hydroxyethyl]carbamoyl}pyrrolidin-1-yl]-2-oxoethyl}carbamoyl)methyl]carbamoyl}-2-carbamoylethyl]carbamoyl}pentyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-carboxypropyl]carbamoyl}-2-methylbutyl]carbamoyl}-2-phenylethyl]carbamoyl}-3-methylbutyl]carbamoyl}-4-carbamimidamidobutyl]carbamoyl}-2-methylpropyl]carbamoyl}ethyl]carbamoyl}-3-carboxypropyl]carbamoyl}-3-carboxypropyl]carbamoyl}-3-carboxypropyl]carbamoyl}-3-(methylsulfanyl)propyl]carbamoyl}-3-carbamoylpropyl]carbamoyl}pentyl]carbamoyl}-2-hydroxyethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-carboxyethyl]carbamoyl}-2-hydroxyethyl]carbamoyl}-2-hydroxypropyl]carbamoyl}-2-phenylethyl]carbamoyl}-2-hydroxypropyl]carbamoyl}methyl)carbamoyl]-4-{2-[(2S)-2-amino-3-(1H-imidazol-4-yl)propanamido]acetamido}butanoic acid
SMILES
CC[[email protected]](C)[[email protected]](NC(=O)[[email protected]](CC1=CC=CC=C1)NC(=O)[[email protected]](CC(C)C)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]@H](NC(=O)[[email protected]](C)NC(=O)[[email protected]](CCC(O)=O)NC(=O)[[email protected]](CCC(O)=O)NC(=O)[[email protected]](CCC(O)=O)NC(=O)[[email protected]](CCSC)NC(=O)[[email protected]](CCC(N)=O)NC(=O)[[email protected]](CCCCN)NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CC(C)C)NC(=O)[[email protected]](CC(O)=O)NC(=O)[[email protected]](CO)NC(=O)[[email protected]@H](NC(=O)[[email protected]](CC1=CC=CC=C1)NC(=O)[[email protected]@H](NC(=O)CNC(=O)[[email protected]](CCC(O)=O)NC(=O)CNC(=O)[[email protected]@H](N)CC1=CNC=N1)[[email protected]@H](C)O)[[email protected]@H](C)O)C(C)C)C(=O)N[[email protected]@H](CCC(O)=O)C(=O)N[[email protected]@H](CC1=CNC2=C1C=CC=C2)C(=O)N[[email protected]@H](CC(C)C)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[[email protected]]1C(=O)N[[email protected]@H](CO)C(=O)N[[email protected]@H](CO)C(=O)NCC(=O)N[[email protected]@H](C)C(=O)N1CCC[[email protected]]1C(=O)N1CCC[[email protected]]1C(=O)N[[email protected]@H](CO)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCCN)C(N)=O

References

General References
  1. Lorenz M, Pfeiffer C, Steinstrasser A, Becker RH, Rutten H, Ruus P, Horowitz M: Effects of lixisenatide once daily on gastric emptying in type 2 diabetes--relationship to postprandial glycemia. Regul Pept. 2013 Aug 10;185:1-8. doi: 10.1016/j.regpep.2013.04.001. Epub 2013 May 9. [PubMed:23665027]
  2. Doyle ME, Egan JM: Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther. 2007 Mar;113(3):546-93. Epub 2006 Dec 28. [PubMed:17306374]
  3. Adlyxin FDA Approval Announcement [Link]
  4. EMA Lixisenatide Assessment [Link]
KEGG Drug
D09729
PubChem Compound
131704317
PubChem Substance
310265161
ChemSpider
17295846
RxNav
1440051
ChEBI
85662
ChEMBL
CHEMBL2108336
Wikipedia
Lixisenatide
AHFS Codes
  • 68:20.06 — Incretin Mimetics
FDA label
Download (1.13 MB)
MSDS
Download (80 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedTreatmentDiabetes Mellitus / Diabetic Kidney Disease / Glucagon-Like Peptide 1 / Nephropathy, Diabetic1
4CompletedTreatmentDiabetes / Type 2 Diabetes Mellitus1
4CompletedTreatmentType 2 Diabetes Mellitus2
4RecruitingTreatmentType 2 Diabetes Mellitus1
4TerminatedTreatmentType 2 Diabetes Mellitus1
4Unknown StatusTreatmentType 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentType 2 Diabetes Mellitus3
3CompletedTreatmentAcute Coronary Syndromes (ACS)1
3CompletedTreatmentType 2 Diabetes Mellitus26

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous100 ug/1mL
Kit; solutionSubcutaneous
SolutionSubcutaneous
Injection
Injection, solutionCutaneous; Parenteral10 MICROGRAMMI
Injection, solutionCutaneous; Parenteral10 μg
Injection, solutionCutaneous; Parenteral20 MICROGRAMMI
Injection, solutionSubcutaneous10 μg
Injection, solutionSubcutaneous20 μg
Injection, solution10 mcg
Injection, solution20 mcg
Solution
Injection, solution100 unit/1mL
SolutionSubcutaneous
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous100 U/mL
SolutionSubcutaneous100 IU
Injection, solutionCutaneous; Parenteral100 U/ML
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9011391No2015-04-212024-03-26US flag
US9233211No2016-01-122024-03-02US flag
US8603044No2013-12-102024-03-02US flag
US8512297No2013-08-202024-09-15US flag
US8679069No2014-03-252025-04-12US flag
US8992486No2015-03-312024-06-05US flag
US8556864No2013-10-152024-03-03US flag
US7918833Yes2011-04-052028-03-23US flag
US9561331No2017-02-072024-08-28US flag
US9623189No2017-04-182024-08-19US flag
US9610409No2017-04-042024-03-02US flag
US9526844No2016-12-272024-03-02US flag
US9604008No2017-03-282024-03-02US flag
US9533105No2017-01-032024-08-17US flag
US9408979No2016-08-092024-03-02US flag
US9604009No2017-03-282024-08-16US flag
US9072836No2015-07-072032-03-15US flag
US9084853No2015-07-212031-10-05US flag
US8882721No2014-11-112031-06-28US flag
US9511193No2016-12-062032-01-19US flag
USRE45313No2014-12-302020-07-12US flag
US8475414No2013-07-022030-12-28US flag
US9308329No2016-04-122030-12-28US flag
US8915888No2014-12-232030-06-08US flag
US9408893No2016-08-092032-08-27US flag
US9526764No2016-12-272029-10-09US flag
US9707176No2017-07-182030-11-11US flag
US9775954No2017-10-032024-03-02US flag
US9827379No2017-11-282024-03-02US flag
US9821032No2017-11-212032-05-09US flag
US9855388No2018-01-022029-04-24US flag
US9440029No2016-09-132032-01-30US flag
US9950039No2018-04-242035-12-10US flag
US9981013No2018-05-292030-08-30US flag
US9717852No2017-08-012033-04-08US flag
US10028910No2018-07-242030-11-11US flag
US10029011No2018-07-242032-08-02US flag
US10117909No2018-11-062029-10-09US flag
US10201663No2019-02-122034-03-10US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP-33ChemAxon
pKa (Strongest Acidic)2.84ChemAxon
pKa (Strongest Basic)11.89ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count78ChemAxon
Hydrogen Donor Count70ChemAxon
Polar Surface Area2060.16 Å2ChemAxon
Rotatable Bond Count169ChemAxon
Refractivity1221.37 m3·mol-1ChemAxon
Polarizability505.8 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
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

Drug created on October 27, 2015 15:41 / Updated on October 25, 2020 09:16

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates