Lixisenatide

Identification

Summary

Lixisenatide is a GLP-1 receptor agonist used for the management of type 2 diabetes mellitus.

Brand Names
Adlyxin Starter Kit, Lyxumia, Soliqua
Generic Name
Lixisenatide
DrugBank Accession Number
DB09265
Background

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type II diabetes mellitus (T2DM). It is sold by Sanofi-Aventis under the brand name Adlyxin in the US3 and Lyxumia in the EU.4 Adlyxin recieved FDA approval July 28, 2016.3

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Protein Chemical Formula
Not Available
Protein Average Weight
4858.0 Da
Sequences
> Lixisenatide Sequence
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK
References:
  1. NIH Inxight Drugs: Lixisenatide [Link]
Download FASTA Format
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

Lixisenatide is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type II diabetes mellitus.5 It is also available in combination with insulin glargine for the same indication.6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used as adjunct in combination to manageType 2 diabetes mellitusCombination Product in combination with: Insulin glargine (DB00047)••••••••••••••••••••••••••• ••••••••
Used as adjunct in combination to manageType 2 diabetes mellitus••••••••••••••••••••••••••• ••••••••
Contraindications & Blackbox Warnings
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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.2 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

Following subcutaneous administration, the median Tmax of lixisenatide ranged from 1-3.5 hours, with no clinically relevant differences in the rate of absorption noted between possible injection sites (i.e. thigh, abdomen, or arm).5

Volume of distribution

The apparent volume of distribution following subcutaneous administration is approximately 100 L.5

Protein binding

Lixisenatide is approximately 55% bound to human plasma proteins.4

Metabolism

Lixisenatide is likely catabolized via non-specific proteolytic degradation.5

Route of elimination

Lixisenatide is presumably eliminated via glomerular filtration and proteolytic degradation.5

Half-life

Following the administration of multiple doses in patients with type II diabetes mellitus, the mean terminal half-life of lixisenatide was approximately 3 hours.5

Clearance

The mean apparent clearance of lixisenatide is approximately 35 L/h.5

Adverse Effects
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Toxicity

Thyroid C-cell adenomas occurred in rats when exposed to >15 times human exposure of 20mcg/day.5 Overdose is associated with GI side effects typical of GLP-1 receptor agonists.

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.
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

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdlyxinInjection, solution100 ug/1mLSubcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUS flag
AdlyxineSolution20 mcg / actSubcutaneousSanofi Aventis2017-09-122023-09-15Canada flag
AdlyxineSolution10 mcg / actSubcutaneousSanofi Aventis2017-09-122023-05-04Canada flag
LyxumiaInjection, solution20 μgSubcutaneousSANOFI WINTHROP INDUSTRIE2016-09-08Not applicableEU flag
LyxumiaInjection, solution20 μgSubcutaneousSANOFI WINTHROP INDUSTRIE2016-09-08Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)Injection, solution; KitSubcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUS flag
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)Injection, solution; KitSubcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUS flag
AdlyxineLixisenatide (0.05 mg / mL) + Lixisenatide (0.1 mg / mL)Kit; SolutionSubcutaneousSanofi Aventis2017-09-122018-10-08Canada flag
AdlyxineLixisenatide (0.05 mg / mL) + Lixisenatide (0.1 mg / mL)Kit; SolutionSubcutaneousSanofi Aventis2017-09-122018-10-08Canada flag
LYXUMIALixisenatide (10 μg) + Lixisenatide (20 μg)Injection, solutionCutaneous; ParenteralSANOFI WINTHROP INDUSTRIE2014-07-08Not applicableItaly flag

Categories

ATC Codes
A10AE54 — Insulin glargine and lixisenatideA10BJ03 — Lixisenatide
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
Not Available

Chemical Identifiers

UNII
74O62BB01U
CAS number
320367-13-3

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. [Article]
  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. [Article]
  3. Adlyxin FDA Approval Announcement [Link]
  4. EMA CHMP Assessment Report: Lyxumia (lixisenatide) [Link]
  5. FDA Approved Drug Products: Adlyxin (lixisenatide) injection for subcutaneous use (Sept 2023) [Link]
  6. FDA Approved Drug Products: Soliqua (insulin glargine and lixisenatide) injection for subcutaneous use (Sept 2023) [Link]
KEGG Drug
D09729
PubChem Compound
131704317
PubChem Substance
310265161
ChemSpider
17295846
RxNav
1440051
ChEBI
85662
ChEMBL
CHEMBL2108336
Wikipedia
Lixisenatide
MSDS
Download (80 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedTreatmentDiabetes Mellitus / Diabetic Kidney Disease (DKD) / Diabetic Nephropathy / Glucagon-Like Peptide 11
4CompletedTreatmentDiabetes / Type 2 Diabetes Mellitus1
4CompletedTreatmentType 2 Diabetes Mellitus4
4RecruitingDiagnosticHealthy Volunteers (HV) / Type 1 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous100 ug/1mL
Injection, solution; kitSubcutaneous
Kit; solutionSubcutaneous
SolutionSubcutaneous10 mcg / act
SolutionSubcutaneous20 mcg / act
Injection
Injection, solutionParenteral; Subcutaneous10 MICROGRAMMI
Injection, solutionParenteral; Subcutaneous20 MICROGRAMMI
Injection, solutionSubcutaneous10 μg
Injection, solutionSubcutaneous20 μg
SolutionSubcutaneous0.15 mg/3ml
SolutionSubcutaneous0.3 mg/3ml
Injection, solution10 mcg
Injection, solutionSubcutaneous10 mcg/0.2ml
Injection, solution20 mcg
Injection, solutionSubcutaneous20 mcg/0.2ml
Injection, solutionSubcutaneous50 mcg/mL
Injection, solutionSubcutaneous0.05 mg/mL
Injection, solutionSubcutaneous100 mcg/mL
SolutionSubcutaneous0.05 mg
SolutionSubcutaneous0.1 mg
Injection, solution
SolutionSubcutaneous
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous100 units/ml
Injection, solutionCutaneous; Parenteral
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

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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insights and accelerate drug research.
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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. Nadkarni P, Chepurny OG, Holz GG: Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23-65. doi: 10.1016/B978-0-12-800101-1.00002-8. [Article]
  2. Lorenz M, Lawson F, Owens D, Raccah D, Roy-Duval C, Lehmann A, Perfetti R, Blonde L: Differential effects of glucagon-like peptide-1 receptor agonists on heart rate. Cardiovasc Diabetol. 2017 Jan 13;16(1):6. doi: 10.1186/s12933-016-0490-6. [Article]
  3. Gallwitz B: Novel Therapeutic Approaches in Diabetes. Endocr Dev. 2016;31:43-56. doi: 10.1159/000439372. Epub 2016 Jan 19. [Article]
  4. Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ: Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017 Apr;19(4):524-536. doi: 10.1111/dom.12849. Epub 2017 Feb 17. [Article]

Drug created at October 27, 2015 21:41 / Updated at October 06, 2023 23:49