Insulin aspart

Identification

Summary

Insulin aspart is a rapid-acting form of insulin used for glycemic control in type 1 and type 2 diabetes mellitus.

Brand Names

Fiasp, Novolog, Novolog Mix, Novomix, Novorapid, Novorapid Penfill, Ryzodeg

Generic Name

Insulin aspart

DrugBank Accession Number

DB01306

Background

Insulin aspart is a rapid-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is typically prescribed for the management of diabetes mellitus to mimic the activity of endogenously produced human insulin, a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.

Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin, such as insulin aspart, to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as Metformin, Gliclazide, or Sitagliptin have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own.

Marketed as the brand name product NovoRapid, insulin aspart begins to exert its effects within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90 minutes after administration. Due to its duration of action of around 5 hours, NovoRapid is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as Insulin detemir, Insulin degludec, and Insulin glargine to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.

Insulin aspart is a recombinant, biosynthetic, fast-acting insulin analogue. Compared to human insulin, it has a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This substitution decreases its propensity to form hexamers and gives it a higher rate of absorption following subcutaneous administration compared to native insulin. Insulin aspart is produced in a genetically modified strain of Saccharomyces cerevisiae (baker's yeast)

Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Hormones / Insulins

Protein Structure

Protein Chemical Formula: C₂₅₆H₃₈₁N₆₅O₇₉S₆
Protein Average Weight: 5825.8 Da

Sequences

>A chain
GIVEQCCTSICSLYQLENYCN

>B chain
FVNQHLCGSHLVEALYLVCGERGFFYTDKT

Download FASTA Format

Synonyms

Aspart
Aspart Insulin
B28-Aspart-Insulin
Insulin aspart
Insulin aspart protamine
Insulin aspart protamine recombinant
Insulin aspart recombinant
Insulin X14
Insulin, aspart protamine, human
Insulin, aspart, human
Insulin,aspart protamine
Insulina asparta

External IDs

INA-X14
NN-1218
NN1218

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Pharmacology

Indication

Insulin aspart is indicated to improve glycemic control in adults and children with diabetes mellitus.^5,6

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Associated Conditions

Indication Type	Indication	Approval Level	Age Group	Dose Form
Management of	Diabetes mellitus	••••••••••••	••••••••••• •••••• •••••••••
Management of	Diabetes mellitus	••• •••		•••••••••• ••••••••
Management of	Diabetes mellitus	••••••••••••		•••••••••• ••••••••
Management of	Diabetes mellitus	••••••••••••	•••••• ••••••••	•••••••••• ••••••••
Management of	Diabetes mellitus	••••••••••••	•••••	•••••••••• ••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours.

Mechanism of action

Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action.

Target	Actions	Organism
AInsulin receptor	agonist	Humans
UInsulin-like growth factor 1 receptor	activator	Humans

Absorption

In studies of healthy volunteers and patients with type 1 diabetes, the median time to maximum concentration of insulin aspart in these trials was 40 to 50 minutes versus 80 to 120 minutes, for regular human insulin respectively. Compared to human insulin, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption.

Volume of distribution

Not Available

Protein binding

Insulin aspart has a low binding affinity to plasma proteins (<10%), similar to that seen with regular human insulin.

Metabolism

Not Available

Route of elimination

Not Available

Half-life

Elimination half-life was found to be 81 minutes (following subcutaneous administration in healthy subjects).

Clearance

1.2 L/h/kg

Adverse Effects

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Toxicity

Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia.

Pathways

Not Available

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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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.

Drug	Interaction
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Acarbose	The risk or severity of hypoglycemia can be increased when Acarbose is combined with Insulin aspart.
Acebutolol	The therapeutic efficacy of Insulin aspart can be increased when used in combination with Acebutolol.
Acetazolamide	The risk or severity of hypoglycemia can be increased when Acetazolamide is combined with Insulin aspart.
Acetohexamide	The risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Insulin aspart.
Acetophenazine	The therapeutic efficacy of Insulin aspart can be decreased when used in combination with Acetophenazine.

Food Interactions

Take with food. Dose adjust as needed. Changes in meal composition may alter the response to insulin aspart.

Products

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International/Other Brands

Novolog FlexPen (Novo Nordisk) / Novolog Penfill (Novo Nordisk)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
.Insulin Aspart Protamine and Insulin Aspart	Injection, suspension	100 [iU]/1mL	Subcutaneous	A-S Medication Solutions	2002-09-11	Not applicable
Fiasp	Injection, solution	100 [iU]/1mL	Subcutaneous	Novo Nordisk	2017-10-20	Not applicable
Fiasp	Injection, solution	100 U/ml	Intravenous; Subcutaneous	Novo Nordisk	2020-12-16	Not applicable
Fiasp	Injection, solution	100 [iU]/1mL	Subcutaneous	Novo Nordisk	2017-10-20	Not applicable
Fiasp	Injection, solution	100 U/ml	Subcutaneous	Novo Nordisk	2020-12-16	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Novomix 30	Insulin aspart (30 unit / mL) + Insulin aspart (70 unit / mL)	Suspension	Subcutaneous	Novo Nordisk	2005-09-12	Not applicable
Novomix 30	Insulin aspart (30 unit / mL) + Insulin aspart (70 unit / mL)	Suspension	Subcutaneous	Novo Nordisk	2005-09-12	Not applicable
Novomix 30 (flexpen)	Insulin aspart (30 %) + Insulin aspart (70 %)	Suspension	Subcutaneous	Novo Nordisk	Not applicable	Not applicable
Novomix 30 (flexpen)	Insulin aspart (30 %) + Insulin aspart (70 %)	Suspension	Subcutaneous	Novo Nordisk	Not applicable	Not applicable
NOVOMIX 30 FLEXPEN INJECTION 100 u/ml	Insulin aspart (70 %) + Insulin aspart (30 %)	Injection	Subcutaneous	NOVO NORDISK PHARMA (SINGAPORE) PTE LTD	2003-06-02	Not applicable

Chemical Identifiers

UNII: D933668QVX
CAS number: 116094-23-6

References

Synthesis Reference

Ronald E. Zimmerman, David John Stokell, Michael Patrick Akers, "ASPART PROINSULIN COMPOSITIONS AND METHODS OF PRODUCING ASPART INSULIN ANALOGS THEREFROM." U.S. Patent US20120214963, issued August 23, 2012.

US20120214963

General References

Heller S, Kurtzhals P, Verge D, Lindholm A: Insulin aspart: promising early results borne out in clinical practice. Expert Opin Pharmacother. 2002 Feb;3(2):183-95. [Article]
Sciacca L, Cassarino MF, Genua M, Pandini G, Le Moli R, Squatrito S, Vigneri R: Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling. Diabetologia. 2010 Aug;53(8):1743-53. doi: 10.1007/s00125-010-1760-6. Epub 2010 Apr 28. [Article]
Home PD: The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences. Diabetes Obes Metab. 2012 Sep;14(9):780-8. doi: 10.1111/j.1463-1326.2012.01580.x. Epub 2012 Mar 9. [Article]
Varewijck AJ, Janssen JA: Insulin and its analogues and their affinities for the IGF1 receptor. Endocr Relat Cancer. 2012 Sep 5;19(5):F63-75. doi: 10.1530/ERC-12-0026. Print 2012 Oct. [Article]
FDA Approved Drug Products: Novolog (insulin aspart) for SC/IV injection [Link]
EMA Approved Drug Products: Truvelog Mix 30 (insulin aspart and protamine-crystallised insulin aspart, 30:70) subcutaneous injection [Link]
FDA Approved Drug Products: Fiasp (insulin aspart) injection for subcutaneous or intravenous administration (June 2023) [Link]

External Links

KEGG Drug: D04475
PubChem Substance: 46507309
RxNav: 51428
ChEMBL: CHEMBL1201496
Therapeutic Targets Database: DAP001092
PharmGKB: PA164784029
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Insulin_aspart

FDA label

Download (909 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Basic Science	Hyperglycemia, Postprandial / Type 2 Diabetes Mellitus	1
4	Completed	Basic Science	Renal Failure, Chronic Renal Failure	1
4	Completed	Diagnostic	Diabetes / Type 1 Diabetes Mellitus / Type 2 Diabetes Mellitus	1
4	Completed	Health Services Research	Type 2 Diabetes Mellitus	1
4	Completed	Prevention	Coronary Artery Disease (CAD)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Novo Nordisk Inc.
Physicians Total Care Inc.

Dosage Forms

Form	Route	Strength
Injection, solution	Subcutaneous	100 [iU]/1mL
Injection, solution	Subcutaneous	600 nmol/ml
Injection, solution	Intravenous; Subcutaneous	600 nmol/ml
Solution	Intravenous; Subcutaneous	100 IU
Injection, solution	Intravenous	100 U/ML
Injection	Subcutaneous	100
Injection, solution	Intravenous; Subcutaneous	100 [iU]/1mL
Injection, suspension	Subcutaneous	100 [iU]/1mL
Injection, suspension	Parenteral; Subcutaneous	100 U/ML
Injection, suspension	Parenteral; Subcutaneous	100 IU/ml
Injection; injection, suspension	Subcutaneous	100 IU/ml
Suspension	Subcutaneous	100 U
Suspension	Subcutaneous	70 %
Injection, suspension	Subcutaneous
Injection	Subcutaneous
Injection	Subcutaneous	100 U/mL
Injection, suspension	Subcutaneous	100 U/ml
Suspension	Subcutaneous	100 U/ml
Injection	Subcutaneous
Injection	Subcutaneous	100 IU/ml
Injection, solution	Intravenous; Parenteral	100 U/ML
Injection, solution	Intravenous; Subcutaneous	100 U/ml
Injection, solution	Parenteral; Subcutaneous	100 U/ML
Solution	Subcutaneous	100 U
Solution	Subcutaneous	100 unit / mL
Injection, solution	Subcutaneous
Injection	Intravenous; Subcutaneous	100 u/ml
Injection, solution	Subcutaneous	100 U/ml
Solution		100 U/ml
Injection	Parenteral	100 U/mL
Solution	Subcutaneous
Injection, solution	Subcutaneous
Injection
Injection, solution	Subcutaneous	180 nmol/ml
Solution	Intravenous; Subcutaneous	100 unit / mL
Injection, solution		100 iu/1ml
Injection, suspension
Suspension	Subcutaneous
Solution		100 iu/1ml

Prices

Unit description	Cost	Unit
Novolog 100 unit/ml cartridge	14.81USD	ml
Novolog mix 70-30 cartridge	10.45USD	ml
Novorapid 100 unit/ml Cartridge	3.89USD	cartridge
Novorapid 100 unit/ml	2.92USD	cartridge

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5618913	No	1997-04-08	2014-06-07
US8672898	Yes	2014-03-18	2022-07-02
US8684969	Yes	2014-04-01	2026-04-20
US9132239	Yes	2015-09-15	2032-08-01
US8920383	Yes	2014-12-30	2027-01-17
US7686786	No	2010-03-30	2026-08-03
US6899699	Yes	2005-05-31	2022-07-01
US5866538	Yes	1999-02-02	2017-12-20
US9108002	Yes	2015-08-18	2026-07-26
USRE41956	Yes	2010-11-23	2021-07-21
US9265893	Yes	2016-02-23	2033-03-23
US6004297	Yes	1999-12-21	2019-07-28
USRE43834	No	2012-11-27	2019-01-28
US7615532	Yes	2009-11-10	2029-12-28
US9486588	Yes	2016-11-08	2022-07-02
US9457154	Yes	2016-10-04	2028-03-27
USRE46363	Yes	2017-04-11	2027-02-03
US9687611	Yes	2017-06-27	2027-08-27
US9775953	Yes	2017-10-03	2027-01-17
US8324157	No	2012-12-04	2030-06-25
US8579869	Yes	2013-11-12	2023-12-30
US7762994	Yes	2010-07-27	2024-11-23
US9884094	No	2018-02-06	2033-05-01
US9861757	Yes	2018-01-09	2026-07-20
US9616180	Yes	2017-04-11	2026-07-20
US10220155	Yes	2019-03-05	2027-01-17
US10357616	No	2019-07-23	2026-01-20
US10376652	No	2019-08-13	2026-01-20

Properties

State: Liquid
Experimental Properties: Not Available

Targets

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Details1. Insulin receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

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

References

Zib I, Raskin P: Novel insulin analogues and its mitogenic potential. Diabetes Obes Metab. 2006 Nov;8(6):611-20. [Article]
De Meyts P: The Insulin Receptor and Its Signal Transduction Network . [Article]

Details2. Insulin-like growth factor 1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Activator

General Function: Protein tyrosine kinase activity
Specific Function: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involv...
Gene Name: IGF1R
Uniprot ID: P08069
Uniprot Name: Insulin-like growth factor 1 receptor
Molecular Weight: 154791.73 Da

References

Varewijck AJ, Janssen JA: Insulin and its analogues and their affinities for the IGF1 receptor. Endocr Relat Cancer. 2012 Sep 5;19(5):F63-75. doi: 10.1530/ERC-12-0026. Print 2012 Oct. [Article]
Vigneri R, Squatrito S, Sciacca L: Insulin and its analogs: actions via insulin and IGF receptors. Acta Diabetol. 2010 Dec;47(4):271-8. doi: 10.1007/s00592-010-0215-3. Epub 2010 Aug 21. [Article]

Enzymes

Details1. Cytochrome P450 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP1A2
Uniprot ID: P05177
Uniprot Name: Cytochrome P450 1A2
Molecular Weight: 58293.76 Da

References

Barnett CR, Wilson J, Wolf CR, Flatt PR, Ioannides C: Hyperinsulinaemia causes a preferential increase in hepatic P4501A2 activity. Biochem Pharmacol. 1992 Mar 17;43(6):1255-61. doi: 10.1016/0006-2952(92)90500-i. [Article]
Pass GJ, Becker W, Kluge R, Linnartz K, Plum L, Giesen K, Joost HG: Effect of hyperinsulinemia and type 2 diabetes-like hyperglycemia on expression of hepatic cytochrome p450 and glutathione s-transferase isoforms in a New Zealand obese-derived mouse backcross population. J Pharmacol Exp Ther. 2002 Aug;302(2):442-50. doi: 10.1124/jpet.102.033553. [Article]
Flockhart Table of Drug Interactions [Link]

Drug created at June 30, 2007 14:44 / Updated at July 01, 2023 10:08

Insulin aspart

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References

Enzymes

References