Insulin lispro

Identification

Summary

Insulin lispro is a modified form of fast-acting insulin used to control hyperglycemia in diabetes mellitus.

Brand Names

Admelog, Humalog, Humalog Mix, Humalog kwikpen, Liprolog, Lyumjev

Generic Name

Insulin lispro

DrugBank Accession Number

DB00046

Background

Insulin lispro is a rapid-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Insulin is 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 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 lispro, 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 cause 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 several oral medications such as Metformin, Gliclazide, or Sitagliptin have been tried, and 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 Humalog, insulin lispro 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, Humalog 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, or 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 lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and was the first commercially available insulin analog. Formerly called LYSPRO from the chemical nomenclature LYS(B28), PRO(B29), insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. These biochemical changes result in a reduced tendency for self-association resulting in dissolution to a dimer and then to a monomer that is absorbed more rapidly after subcutaneous injection compared to endogenous human insulin.

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: C₂₅₇H₃₈₇N₆₅O₇₆S₆
Protein Average Weight: 5808.0 Da

Sequences

>A chain
GIVEQCCTSICSLYQLENYCN

>B chain
FVNQHLCGSHLVEALYLVCGERGFFYTKPT

Download FASTA Format

Synonyms

Insulin lispro
Insulin lispro (genetical recombination)
Insulin lispro (rDNA origin)
Insulin lispro protamine
Insulin lispro protamine recombinant
Insulin lispro recombinant
insulin lispro-aabc
Insulin,lispro,human/rDNA
Insulin,lispro,protamine/rDNA
Insulina lispro

External IDs

LY-275585
LY275585
SAR-342434
SAR342434

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Pharmacology

Indication

Insulin lispro is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.⁹

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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	••••••••••••		•••••••••• ••••••••
Treatment of	Diabetes mellitus	••• •••	••••••••	•••••••••
Treatment 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. Increased insulin secretion following meals is 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 lispro is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin lispro is 10-15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 4-5 hours. Compared to regular human insulin, insulin lispro has a more rapid onset of action and a shorter duration of action. Insulin lispro is also shown to be equipotent to human insulin on a molar basis.

Insulin lispro has been shown to be equipotent to human insulin on a molar basis. One unit of insulin lispro has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that insulin lispro has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.⁹

The pharmacodynamics of a single 20 unit dose of insulin lispro at 200 units/mL (HUMALOG U-200) administered subcutaneously were compared to the pharmacodynamics of a single 20 unit dose of insulin lispro at 100 units/mL (HUMALOG U-100) administered subcutaneously in a euglycemic clamp study enrolling healthy subjects. In this study, the overall, maximum, and time to maximum glucose lowering effect were similar between HUMALOG U-200 and HUMALOG U-100. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) were 125 g and 126 g for HUMALOG U-200 and HUMALOG U-100, respectively. The maximum glucose infusion rate was 534 mg/min and 559 mg/min and the corresponding median time (min, max) to maximum effect were 2.8 h (0.5 h – 6.3 h) and 2.4 h (0.5 h – 4.7 h) for HUMALOG U-200 and HUMALOG U-100, respectively.⁹

Mechanism of action

Insulin lispro 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. Reversal of the proline and lysine residues at positions B28 and B29 of native insulin eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of the insulin dimers that comprise insulin hexamers. Hexamers of insulin lispro are produced in the presence of zinc and m-cresol. These weakly associated hexamers quickly dissociate upon subcutaneous injection and are absorbed as monomers through vascular endothelial cells. These properties give insulin lispro its fast-acting properties.

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

Absorption

Studies in healthy volunteers and patients with diabetes demonstrated that insulin lispro is absorbed more quickly than regular human insulin, specifically at the abdominal, deltoid, or femoral subcutaneous sites. In healthy volunteers given subcutaneous doses of insulin lispro ranging from 0.1 to 0.4 unit/kg, peak serum levels were seen 30 to 90 minutes after dosing. When healthy volunteers received equivalent doses of regular human insulin, peak insulin levels occurred between 50 to 120 minutes after dosing. After insulin lispro was administered in the abdomen, serum drug levels were higher, and the duration of action was slightly shorter than after deltoid or thigh administration.⁹

Bioavailability of insulin lispro is similar to that of regular human insulin. The absolute bioavailability after subcutaneous injection ranges from 55% to 77% with doses between 0.1 to 0.2 unit/kg, inclusive.⁹

The mean observed area under the serum insulin concentration-time curve from time zero to infinity was 2360 pmol hr/L to 2390 pmol hr/L. The corresponding mean peak serum insulin concentration was 795 pmol/L to 909 pmol/L, and the median time to maximum concentration was 1.0 hour.⁹

Volume of distribution

When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of HUMALOG appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively) in contrast to that of regular human insulin for which, the volume of distribution was comparable across the two dose groups (1.37 and 1.12 L/kg for 0.1 and 0.2 U/kg dose, respectively).⁹

Protein binding

Not Available

Metabolism

Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of insulin lispro is identical to that of regular human insulin.⁹

Route of elimination

Not Available

Half-life

After subcutaneous administration of insulin lispro, the t_1/2 is shorter than that of regular human insulin (1 versus 1.5 hours, respectively).⁹ For intravenous administration, insulin lispro demonstrated a mean t_1/2 of 0.85 hours (51 minutes) and 0.92 hours (55 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses, and regular human insulin mean t1/2 was 0.79 hours (47 minutes) and 1.28 hours (77 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses.⁹

Clearance

When administered intravenously, insulin lispro and regular human insulin demonstrated similar dose-dependent clearance, with a mean clearance of 21.0 mL/min/kg and 21.4 mL/min/kg, respectively (0.1 unit/kg dose), and 9.6 mL/min/kg and 9.4 mL/min/kg, respectively (0.2 unit/kg dose).⁹

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. Rare cases of lipoatrophy or lipohypertrophy reactions have been observed.

Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.⁹

Patients with renal or hepatic impairment may be at increased risk of hypoglycemia and may require more frequent insulin lispro dose adjustment and more frequent blood glucose monitoring.⁹

Standard 2-year carcinogenicity studies in animals have not been performed. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area). Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose.⁹

Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays.⁹

Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats. In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.⁹

Pathways

Not Available

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Not Available

Interactions

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

Food Interactions

No interactions found.

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Admelog	Injection, solution	100 U/1mL	Intravenous; Subcutaneous	sanofi-aventis U.S. LLC	2017-12-11	Not applicable
Admelog	Solution	100 unit / mL	Subcutaneous	Sanofi Aventis	2019-11-22	Not applicable
Admelog	Injection, solution	100 U/1mL	Intravenous; Subcutaneous	sanofi-aventis U.S. LLC	2018-10-19	Not applicable
Admelog	Injection, solution	100 U/1mL	Intravenous; Subcutaneous	REMEDYREPACK INC.	2019-10-30	Not applicable
Admelog	Injection, solution	100 U/1mL	Subcutaneous	sanofi-aventis U.S. LLC	2017-12-11	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Humalog Mix 25 (cartridge)	Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL)	Suspension	Subcutaneous	Eli Lilly & Co. Ltd.	1999-07-05	Not applicable
Humalog Mix 25 (cartridge)	Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL)	Suspension	Subcutaneous	Eli Lilly & Co. Ltd.	1999-07-05	Not applicable
Humalog Mix 25 (kwikpen)	Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL)	Suspension	Subcutaneous	Eli Lilly & Co. Ltd.	2013-09-30	Not applicable
Humalog Mix 25 (kwikpen)	Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL)	Suspension	Subcutaneous	Eli Lilly & Co. Ltd.	2013-09-30	Not applicable
Humalog Mix 25 (pen)	Insulin lispro (25 unit / mL) + Insulin lispro (75 unit / mL)	Suspension	Subcutaneous	Eli Lilly & Co. Ltd.	2000-01-10	2011-04-29

Chemical Identifiers

UNII: GFX7QIS1II
CAS number: 133107-64-9

References

General References

Miles HL, Acerini CL: Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus. Paediatr Drugs. 2008;10(3):163-76. [Article]
Zib I, Raskin P: Novel insulin analogues and its mitogenic potential. Diabetes Obes Metab. 2006 Nov;8(6):611-20. [Article]
Holleman F, Hoekstra JB: Insulin lispro. N Engl J Med. 1997 Jul 17;337(3):176-83. doi: 10.1056/NEJM199707173370307. [Article]
Candido R, Wyne K, Romoli E: A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus. Diabetes Ther. 2018 Jun;9(3):927-949. doi: 10.1007/s13300-018-0422-4. Epub 2018 Apr 13. [Article]
Brems DN, Alter LA, Beckage MJ, Chance RE, DiMarchi RD, Green LK, Long HB, Pekar AH, Shields JE, Frank BH: Altering the association properties of insulin by amino acid replacement. Protein Eng. 1992 Sep;5(6):527-33. [Article]
Howey DC, Bowsher RR, Brunelle RL, Woodworth JR: [Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin. Diabetes. 1994 Mar;43(3):396-402. [Article]
Torlone E, Fanelli C, Rambotti AM, Kassi G, Modarelli F, Di Vincenzo A, Epifano L, Ciofetta M, Pampanelli S, Brunetti P, et al.: Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. Diabetologia. 1994 Jul;37(7):713-20. [Article]
HUMALOG FDA Label [Link]
FDA Approved Drug Products: HUMALOG (insulin lispro) injection, for subcutaneous or intravenous use (July 2023) [Link]
FDA Approved Drug Products: HUMALOG® Mix50/50TM (50% INSULIN LISPRO PROTAMINE AND 50% INSULIN LISPRO) INJECTION [Link]
FDA Approved Drug Products: HUMALOG® Mix75/25TM (75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO) INJECTION [Link]

External Links

KEGG Drug: D04477
PubChem Substance: 46507498
RxNav: 314684
ChEMBL: CHEMBL1201538
Therapeutic Targets Database: DNC000800
PharmGKB: PA164747059
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Insulin_lispro

FDA label

Download (1.13 MB)

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	Not Available	Type 2 Diabetes Mellitus	1
4	Completed	Prevention	Coronary Artery Disease (CAD)	1
4	Completed	Prevention	Diabetic Nephropathy	1
4	Completed	Prevention	Hyperglycemia	2
4	Completed	Treatment	Acute Myocardial Infarction (AMI) / Type 2 Diabetes Mellitus	1

Pharmacoeconomics

Manufacturers

Eli lilly and co

Packagers

Eli Lilly & Co.
Hospira Inc.
Lilly Del Caribe Inc.
Midwest IV and Home Care
Physicians Total Care Inc.

Dosage Forms

Form	Route	Strength
Injection, solution	Intravenous; Subcutaneous	100 U/1mL
Injection, solution	Subcutaneous	100 U/1mL
Solution	Subcutaneous	100 unit / mL
Solution	Intravenous; Subcutaneous	100 U
Injection, solution		40 U/ML
Injection, solution	Intramuscular; Parenteral; Subcutaneous	100 U/ML
Injection, solution	Intramuscular; Parenteral; Subcutaneous	200 U/ML
Injection, solution	Intravenous	100 U/ML
Injection, solution	Intravenous; Subcutaneous	100 U/ML
Injection, solution	Intravenous; Subcutaneous	100 [iU]/1mL
Injection, solution	Subcutaneous	100 [iU]/1mL
Injection, solution	Subcutaneous	200 U/ML
Injection, suspension	Intramuscular; Parenteral; Subcutaneous	100 U/ML
Injection, suspension	Parenteral; Subcutaneous	100 U/ML
Injection, suspension	Parenteral; Subcutaneous	100 IU/ml
Injection, suspension	Subcutaneous	100
Solution		100 iu/1ml
Solution	Subcutaneous	100 UI
Solution	Subcutaneous	100 U/ml
Solution	Intramuscular; Intravenous; Subcutaneous	100 unit / mL
Suspension	Parenteral	3.5 mg
Solution	Subcutaneous	100 iu/ml
Solution	Intravenous; Subcutaneous	3.5 mg
Solution	Subcutaneous	200 unit / mL
Injection	Subcutaneous	100 iu/ml
Injection	Intravenous; Subcutaneous
Injection, solution	Intravenous; Subcutaneous	100 iu/1ml
Injection, solution	Subcutaneous	200 [iU]/1mL
Injection	Intravenous; Subcutaneous	100 iu/ml
Injection	Subcutaneous	200 U/mL
Suspension		100 iu/1ml
Suspension	Subcutaneous
Injection, suspension	Subcutaneous	100 IU/mL
Injection, suspension	Subcutaneous	100 U/mL
Injection, suspension		100 iu/1ml
Injection	Subcutaneous
Injection	Subcutaneous
Injection, suspension	Subcutaneous	100 [iU]/1mL
Liquid	Intramuscular; Intravenous; Subcutaneous	100 unit / mL
Injection, solution	Intramuscular; Subcutaneous	100 U/ML
Injection, solution	Parenteral; Subcutaneous	100 U/ML
Injection, solution		100 U/ml
Injection, solution		200 U/ml
Injection, solution	Subcutaneous	100 U/ML
Solution	Intravenous; Subcutaneous	100 unit / mL
Solution	Intravenous; Subcutaneous	300 unit / 3 mL
Solution	Subcutaneous	200 U
Solution	Subcutaneous	600 unit / 3 mL

Prices

Unit description	Cost	Unit
HumaLOG KwikPen 100 unit/ml Solution (1box = 5 Pens = 15ml)	240.18USD	box
HumaLOG Mix 50/50 KwikPen 50-50% Suspension Five 3ml Pens Per Box = 15ml	240.18USD	box
HumaLOG Mix 75/25 KwikPen 75-25% Suspension Five 3ml Pen Per Box = 15ml	240.18USD	box
HumaLOG Mix 75/25 Pen 75-25% Suspension 15ml Box	240.18USD	box
HumaLOG Pen (five 3ml Pens Per Box) 15ml Box	240.18USD	box
HumaLOG 100 unit/ml Solution 1 Box = Five 3ml Cartridges = 15ml	231.0USD	box
HumaLOG 100 unit/ml Solution 10ml Vial	124.36USD	vial
Humalog 100 unit/ml kwikpen	15.4USD	ml
Humalog 100 unit/ml pen	15.4USD	ml
Humalog mix 50-50 kwikpen	15.4USD	ml
Humalog mix 50-50 pen	15.4USD	ml
Humalog mix 50/50 kwikpen	11.83USD	ml
Humalog 100 unit/ml Cartridge	9.37USD	cartridge
Humalog 100 unit/ml	2.95USD	cartridge

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

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5474978	No	1995-12-12	2014-06-16
US5514646	No	1996-05-07	2013-05-07
CA2151564	No	2003-02-11	2015-06-12
CA2151560	No	2000-05-09	2015-06-12
US9011391	No	2015-04-21	2024-03-26
US7291132	No	2007-11-06	2024-08-09
US9233211	No	2016-01-12	2024-03-02
US8603044	No	2013-12-10	2024-03-02
US8512297	No	2013-08-20	2024-09-15
US8679069	No	2014-03-25	2025-04-12
US8992486	No	2015-03-31	2024-06-05
US8556864	No	2013-10-15	2024-03-03
US7918833	Yes	2011-04-05	2028-03-23
US6551992	No	2003-04-22	2018-06-11
US6034054	No	2000-03-07	2018-06-11
US9561331	No	2017-02-07	2024-08-28
US9623189	No	2017-04-18	2024-08-19
US9610409	No	2017-04-04	2024-03-02
US9526844	No	2016-12-27	2024-03-02
US9604008	No	2017-03-28	2024-03-02
US9533105	No	2017-01-03	2024-08-17
US9408979	No	2016-08-09	2024-03-02
US9604009	No	2017-03-28	2024-08-16
US9775954	No	2017-10-03	2024-03-02
US9827379	No	2017-11-28	2024-03-02
US9717852	No	2017-08-01	2033-04-08

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	81 °C	Khachidze, D.G. et al., J. Biol. Phys. Chem. 1:64-67 (2001)
hydrophobicity	0.218	Not Available
isoelectric point	5.39	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

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Jehle PM, Fussgaenger RD, Kunze U, Dolderer M, Warchol W, Koop I: The human insulin analog insulin lispro improves insulin binding on circulating monocytes of intensively treated insulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab. 1996 Jun;81(6):2319-27. [Article]
Jehle PM, Fussganger RD, Seibold A, Luttke B, Bohm BO: Pharmacodynamics of insulin Lispro in 2 patients with type II diabetes mellitus. Int J Clin Pharmacol Ther. 1996 Nov;34(11):498-503. [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]
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]
Sarfstein R, Nagaraj K, LeRoith D, Werner H: Differential Effects of Insulin and IGF1 Receptors on ERK and AKT Subcellular Distribution in Breast Cancer Cells. Cells. 2019 Nov 23;8(12). pii: cells8121499. doi: 10.3390/cells8121499. [Article]
Donner T, Sarkar S: Insulin - Pharmacology, Therapeutic Regimens, and Principles of Intensive Insulin Therapy . [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]

Details2. Insulin-degrading enzyme

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

General Function: Zinc ion binding
Specific Function: Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by A...
Gene Name: IDE
Uniprot ID: P14735
Uniprot Name: Insulin-degrading enzyme
Molecular Weight: 117967.49 Da

References

Bennett RG, Fawcett J, Kruer MC, Duckworth WC, Hamel FG: Insulin inhibition of the proteasome is dependent on degradation of insulin by insulin-degrading enzyme. J Endocrinol. 2003 Jun;177(3):399-405. doi: 10.1677/joe.0.1770399. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Insulin lispro

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

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Clinical Trials

Pharmacoeconomics

Properties

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References

Enzymes

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References