Identification

Name
Insulin Degludec
Accession Number
DB09564
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones / Insulins
Description

Insulin Degludec is an ultra-long-acting insulin analogue used for glycemic control in Diabetes Mellitus. Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake and by preventing hepatic glucose production. Compared to endogenous insulin, this product has an added hexadecanedioic acid to lysine at the B29 position which allows for the formation of multi-hexamers. When injected subcutaneously, these multi-hexamers form a drug depot store from which monomers are slowly and continuously absorbed into the circulation. As a result, Insulin Degludec has a protracted time action profile due to the delayed absorption from subcutaneous tissue depots into the systemic circulation. Compared to available long-acting analogues such as insulin glargine and insulin detemir, which have a duration of action of 20-24 hours, insulin degludec provides a consistent level of basal insulin over 42 hours with a low peak:trough ratio. Limitations of shorter acting analogues include more frequent dosing and less stable pharmacokinetics, which may negatively impact patient adherence and glucose control, particularly nocturnal control.

Insulin Degludec was approved by the FDA in September 2015 as the product Tresiba, for use in providing glycemic control to adults with diabetes mellitus.

Protein structure
Db09564
Protein chemical formula
C274H411N65O81S6
Protein average weight
6103.97 Da
Sequences
>A Chain
FVNQHLCGSHLVEALYLVCGERGFFYTPK
>B Chain
GIVEQCCTSICSLYQLENYCN
Download FASTA Format
Synonyms
  • Insulina degludec
External IDs
NN-1250 / NN1250
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TresibaInjection, solution100 U/mlSubcutaneousNovo Nordisk2013-01-21Not applicableEu
TresibaInjection, solution200 U/1mLSubcutaneousA-S Medication Solutions2015-09-25Not applicableUs
TresibaInjection, solution100 U/mlSubcutaneousNovo Nordisk2013-01-21Not applicableEu
TresibaSolution100 unitSubcutaneousNovo Nordisk2017-09-15Not applicableCanada
TresibaInjection, solution200 U/mlSubcutaneousNovo Nordisk2013-01-21Not applicableEu
TresibaInjection, solution200 U/mlSubcutaneousNovo Nordisk2013-01-21Not applicableEu
TresibaInjection, solution200 U/mlSubcutaneousNovo Nordisk2013-01-21Not applicableEu
TresibaInjection, solution200 U/1mLSubcutaneousNovo Nordisk2015-09-25Not applicableUs
TresibaInjection, solution100 U/mlSubcutaneousNovo Nordisk2013-01-21Not applicableEu
TresibaSolution100 unitSubcutaneousNovo NordiskNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
RyzodegInsulin Degludec (2.56 mg/ml) + Insulin Aspart (1.05 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2013-01-21Not applicableEu
Ryzodeg 70/30Insulin Degludec (70 U/1mL) + Insulin Aspart (30 U/1mL)Injection, solutionSubcutaneousNovo Nordisk2018-01-012018-01-01Us
XultophyInsulin Degludec (100 U/ml) + Liraglutide (3.6 mg/ml)Injection, solutionSubcutaneousNovo Nordisk2014-09-18Not applicableEu
XultophyInsulin Degludec (100 unit) + Liraglutide (3.6 mg)SolutionSubcutaneousNovo NordiskNot applicableNot applicableCanada
Categories
UNII
54Q18076QB
CAS number
844439-96-9

Pharmacology

Indication

Insulin degludec is indicated to improve glycemic control in adults with diabetes mellitus.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake and by preventing hepatic glucose production. Compared to endogenous insulin, Insulin Degludec has an added hexadecanedioic acid to lysine at the B29 position which allows for the formation of multi-hexamers in subcutaneous tissues. When injected subcutaneously, these multi-hexamers form a drug depot store that slowly release. As a result, Insulin Degludec has a protracted time action profile due to the delayed absorption from subcutaneous tissue depots into the systemic circulation

TargetActionsOrganism
AInsulin receptor
ligand
Human
Absorption

In patients with type 1 diabetes, after 8 days of once daily subcutaneous dosing with 0.4 U/kg, maximum degludec concentrations of 4472 pmol/L were attained at a median of 9 hours (tmax). After the first dose of, median onset of appearance was around one hour. The glucose lowering effect lasted at least 42 hours after the last of 8 once-daily injections. Insulin degludec concentration reach steady state levels after 3-4 days.

Volume of distribution
Not Available
Protein binding

The affinity of insulin degludec to serum albumin corresponds to a plasma protein binding of >99% in human plasma.

Metabolism

All insulin degludec metabolites are inactive.

Route of elimination
Not Available
Half life

The half-life after subcutaneous administration is determined primarily by the rate of absorption from the subcutaneous tissue. On average, the half-life at steady state is approximately 25 hours independent of dose.

Clearance

0.03 L/kg

Toxicity

Observe for signs and symptoms of hypoglycemia, hypokalemia, and fluid retention and heart failure with concomitant use of Thiazolidinediones. Pregnancy Category C

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Insulin Degludec is combined with 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Insulin Degludec can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Insulin Degludec.
AcebutololAcebutolol may increase the hypoglycemic activities of Insulin Degludec.
AcetazolamideThe therapeutic efficacy of Insulin Degludec can be increased when used in combination with Acetazolamide.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Insulin Degludec.
Acetyl sulfisoxazoleThe therapeutic efficacy of Insulin Degludec can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Insulin Degludec.
AgmatineThe risk or severity of hypoglycemia can be increased when Agmatine is combined with Insulin Degludec.
AICA ribonucleotideThe risk or severity of hypoglycemia can be increased when AICA ribonucleotide is combined with Insulin Degludec.
Food Interactions
Not Available

References

General References
  1. Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Munoz-Torres M, Rosenstock J, Endahl LA, Francisco AM, Hollander P: Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012 Apr 21;379(9825):1498-507. doi: 10.1016/S0140-6736(12)60205-0. [PubMed:22521072]
  2. Wang F, Surh J, Kaur M: Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review. Diabetes Metab Syndr Obes. 2012;5:191-204. doi: 10.2147/DMSO.S21979. Epub 2012 Jul 5. [PubMed:22826637]
  3. Haahr H, Heise T: A review of the pharmacological properties of insulin degludec and their clinical relevance. Clin Pharmacokinet. 2014 Sep;53(9):787-800. doi: 10.1007/s40262-014-0165-y. [PubMed:25179915]
  4. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U: Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res. 2012 Aug;29(8):2104-14. doi: 10.1007/s11095-012-0739-z. Epub 2012 Apr 7. [PubMed:22485010]
External Links
KEGG Drug
D09727
PubChem Substance
347910463
ChEMBL
CHEMBL2107869
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
A10AE56 — Insulin degludec and liraglutideA10AD06 — Insulin degludec and insulin aspartA10AE06 — Insulin degludec
AHFS Codes
  • 68:20.08 — Insulins
FDA label
Download (7.77 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
1CompletedTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 117
1CompletedTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 1 / Type 2 Diabetes Mellitus3
1CompletedTreatmentDiabetes Mellitus (DM) / Healthy Volunteers12
1CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus5
1Not Yet RecruitingBasic ScienceHealthy Volunteers1
1TerminatedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 12
2CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
2Not Yet RecruitingTreatmentType 2 Diabetes Mellitus1
2, 3Not Yet RecruitingTreatmentType 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 11
3Active Not RecruitingTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus3
3Active Not RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
3Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
3CompletedTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 17
3CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus24
3Not Yet RecruitingTreatmentDiabetes Mellitus (DM)1
3RecruitingTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 11
3RecruitingTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
4Active Not RecruitingTreatmentDiabetes, Diabetes Mellitus Type 1 / Nocturnal Hypoglycemia / Recurrent Severe Hypoglycaemia1
4CompletedTreatmentType 2 Diabetes Mellitus4
4Not Yet RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
4Not Yet RecruitingTreatmentType2 Diabetes1
4RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
4RecruitingTreatmentType 2 Diabetes Mellitus3
Not AvailableActive Not RecruitingNot AvailableDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 1 / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 1 / Type 2 Diabetes Mellitus3
Not AvailableCompletedNot AvailableDiabetes, Diabetes Mellitus Type 11
Not AvailableEnrolling by InvitationNot AvailableDiabetes Mellitus (DM)1
Not AvailableNot Yet RecruitingNot AvailableDiabetes, Diabetes Mellitus Type 1 / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous100 U/ml
Injection, solutionSubcutaneous100 U/1mL
Injection, solutionSubcutaneous200 U/ml
Injection, solutionSubcutaneous200 U/1mL
SolutionSubcutaneous100 unit
SolutionSubcutaneous200 unit
Injection, solutionSubcutaneous
SolutionSubcutaneous
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8672898No2014-03-182022-01-02Us
US8684969No2014-04-012025-10-20Us
US9132239No2015-09-152032-02-01Us
US8920383No2014-12-302026-07-17Us
US7686786No2010-03-302026-08-03Us
US6899699No2005-05-312022-01-02Us
US5866538Yes1999-02-022017-12-20Us
US9108002No2015-08-182026-01-20Us
US6458924No2002-10-012017-08-22Us
US6268343No2001-07-312022-08-22Us
US8846618No2014-09-302022-06-27Us
US7235627No2007-06-262017-08-22Us
US7615532No2009-11-102025-05-25Us
US9486588No2016-11-082022-01-02Us
US9457154No2016-10-042027-09-27Us
USRE46363No2017-04-112026-08-03Us
US8937042No2015-01-202029-05-05Us
US9687611No2017-06-272027-02-27Us
US9775953No2017-10-032026-07-17Us
US9884094No2018-02-062033-05-01Us
US9861757No2018-01-092026-01-20Us
US9616180No2017-04-112026-01-20Us

Properties

State
Not Available
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
Human
Pharmacological action
Yes
Actions
Ligand
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (...
Gene Name
INSR
Uniprot ID
P06213
Uniprot Name
Insulin receptor
Molecular Weight
156331.465 Da

Drug created on November 30, 2015 12:10 / Updated on November 20, 2018 00:59