insulin glargine

WordNet

1. hormone secreted by the isles of Langerhans in the pancreas; regulates storage of glycogen in the liver and accelerates oxidation of sugar in cells

PrepTutorEJDIC

1. インシュリン(膵臓(すいぞう)ホルモンで糖尿病治療剤)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/08 13:44:58」(JST)

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Insulin glargine

Systematic (IUPAC) name
Recombinant human insulin
Clinical data
Trade names	Lantus, Toujeo, other
AHFS/Drugs.com	Monograph
MedlinePlus	a600027
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Subcutaneous
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Identifiers
CAS Number	160337-95-1 Y
ATC code	A10AE04 (WHO)
IUPHAR/BPS	7572
DrugBank	DB00047 Y
ChemSpider	none
UNII	2ZM8CX04RZ N
KEGG	D03250 Y
Chemical data
Formula	C267H404N72O78S6
Molar mass	6063 g/mol
NY (what is this?)  (verify)

Insulin glargine, marketed under the names Lantus among others, is a long-acting basal insulin analogue, given once daily to help control the blood sugar level of those with diabetes. It consists of microcrystals that slowly release insulin, giving a long duration of action of 18 to 26 hours, with a "peakless" profile (according to the insulin glargine package insert). Pharmacokinetically, it resembles basal insulin secretion of non-diabetic pancreatic beta cells. Sometimes, in type 2 diabetes and in combination with a short acting sulfonylurea (drugs which stimulate the pancreas to make more insulin), it can offer moderate control of serum glucose levels. In the absence of endogenous insulin—type 1 diabetes, depleted type 2 (in some cases) or latent autoimmune diabetes of adults in late stage—insulin glargine needs the support of fast acting insulin taken with food to reduce the effect of prandially derived glucose.

Medical uses

The long acting insulins, which includes insulin glargine, do not appear much better than neutral protamine Hagedorn (NPH) insulin but have a significantly greater cost making them, as of 2010, not cost effective. It is unclear if there is a difference in hypoglycemia and not enough data to determine any differences with respect to long term outcomes.

Mixing with other insulins

Unlike some other longer-acting insulins, glargine must not be diluted or mixed with other insulin or solution in the same syringe. However, this restriction has been questioned.

Adverse effects

Cancer

As of 2012 tentative evidence shows no association between insulin glargine and cancer. Previous studies had raised concerns.

Pharmacology

Mechanism of action

Insulin glargine has a substitution of glycine for asparagine at N21 (Asn21) and two arginines added to the carboxy terminal of B chain. The arginine amino acids shifts the isoelectric point from a pH of 5.4 to 6.7, making the molecule more soluble at an acidic pH and less soluble at physiological pH. The isoelectric shift also allows for the subcutaneous injection of a clear solution. The glycine substitution prevents deamidation of the acid-sensitive asparagine at acidic pH. In the neutral subcutaneous space, higher-order aggregates form, resulting in a slow, peakless dissolution and absorption of insulin from the site of injection. It can achieve a peakless level for at least 24 hours.

Acceptance and repartition in the body

Insulin glargine is formulated at an acidic pH 4, where it is completely water-soluble. After subcutaneous injection of the acidic solute (which can cause discomfort and a stinging sensation), when a physiologic pH (approximately 7.4) is achieved the increase in pH causes the insulin to come out of solution resulting in the formation of higher order aggregates of insulin hexamers. The higher order aggregation slows the dissociation of the hexamers into insulin monomers, the functional and physiologically active unit of insulin. This gradual process ensures that small amounts of insulin glargine are released into the body continuously, giving an almost peakless profile.

History

The development of insulin glargine was conducted at Sanofi-Aventis's biotechnology competence center in Frankfurt-Höchst. Sanofi supplies the product to over 100 countries and more than 3,5 million patients worldwide. This makes Lantus Germany's largest and most important export pharmaceutical product. Sanofi-Aventis increased its turn-over with Lantus around 28% to 2,45 Billion €, therefrom 130 Million € in Germany, where approx. 1.8 million people with diabetes use the product. In 2007 Lantus was the 15th highest selling pharmaceutical product in Germany.

The investment in the production of Lantus and insulin-pen-manufacturing in Frankfurt-Höchst cost 700 Million €. In 2008 a new manufacturing plant was established for further insulin-pen manufacturing with an investment of 150 Million €. At Sanofi-Aventis the production of Lantus created 3000 jobs in Berlin and Frankfurt-Höchst.

On June 9, 2000 the European Commission formally approved the launching of Lantus by Sanofi-Aventis Germany Ltd. in the entire European Union. The admission was prolonged on June 9, 2005.

A three-fold more concentrated formulation, brand name Toujeo, was introduced after FDA approval in 2015.

Patent expiry

Patent protection for insulin glargine expired in most countries in 2015. Biosimilar insulin glargine from competitor Eli Lilly became available in most countries during 2015, under the brand names Basaglar and Abasaglar. Biosimilar insulin glargine has only been released in 100U/mL strength to date, and biosimilar equivalents in the 300U/mL strength of Toujeo are yet to launch.

See also

• Insulin detemir
• Insulin degludec

References

External links

• Insulin glargine - MedlinePlus
• Lantus website (Sanofi-Aventis)
• Lantus: further information on product characteristics, dosage and studies
• U.S. National Library of Medicine: Drug Information Portal - Insulin glargine
• Comparing Insulins Detemir and Glargine in Type 2 Diabetes: More Similarities than Differences

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. Insulin: Drug formulations
• 2. 糖尿病におけるインスリン療法の一般原則 general principles of insulin therapy in diabetes mellitus
• 3. 2型糖尿病におけるインスリン療法 insulin therapy in type 2 diabetes mellitus
• 4. 成人の1型糖尿病における血糖値マネージメント management of blood glucose in adults with type 1 diabetes mellitus
• 5. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus

English Journal

• Antidiabetic drugs restore abnormal transport of amyloid-β across the blood-brain barrier and memory impairment in db/db mice.

• Chen F1, Dong RR1, Zhong KL1, Ghosh A1, Tang SS1, Long Y1, Hu M1, Miao MX1, Liao JM1, Sun HB1, Kong LY1, Hong H2.
• Neuropharmacology.Neuropharmacology.2016 Feb;101:123-36. doi: 10.1016/j.neuropharm.2015.07.023. Epub 2015 Jul 26.
• Previous studies have shown significant changes in amyloid-β (Aβ) transport across the blood-brain barrier (BBB) under diabetic conditions with hypoinsulinemia, which is involved in diabetes-associated cognitive impairment. Present study employed db/db mice with hyperinsulinemia to investigate cha
• PMID 26211973

• Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

• Sreenivas S1, Krishnaiah SM2, Shyam Mohan AH3, Mallikarjun N3, Govindappa N3, Chatterjee A3, Sastry KN3.
• Protein expression and purification.Protein Expr Purif.2016 Feb;118:1-9. doi: 10.1016/j.pep.2015.10.002. Epub 2015 Oct 22.
• Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over
• PMID 26470649

• Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5.

• Buse JB1, Rodbard HW2, Trescoli Serrano C3, Luo J4, Ivanyi T4, Bue-Valleskey J4, Hartman ML4, Carey MA5, Chang AM6; IMAGINE 5 Investigators.
• Diabetes care.Diabetes Care.2016 Jan;39(1):92-100. doi: 10.2337/dc15-1531. Epub 2015 Nov 17.
• OBJECTIVE: To evaluate the efficacy and safety of basal insulin peglispro (BIL) versus insulin glargine in patients with type 2 diabetes (hemoglobin A1c [HbA1c] ≤9% [75 mmol/mol]) treated with basal insulin alone or with three or fewer oral antihyperglycemic medications.RESEARCH DESIGN AND METHODS
• PMID 26577417

Japanese Journal

• Efficacy of switching from premix analog insulin twice daily injection to insulin glargine once daily injection with sitagliptin

• Takahashi Hideo,Sakai Koji,Kawanishi Kunio [他]
• Diabetology international 6(1), 33-38, 2015
• NAID 40020406067

• An Open-label Longitudinal Study on the Efficacy of Switching from Insulin Glargine or Detemir to Degludec in Type 2 Diabetes Mellitus

• Kanazawa Ippei,Notsu Masakazu,Tanaka Ken-ichiro,Kiyohara Nobuaki,Tada Yuko,Sugimoto Toshitsugu
• Internal Medicine 54(13), 1591-1598, 2015
• … Objective Insulin degludec (IDeg), a new long-acting basal insulin, and FlexTouch, a new injection device, recently became available in Japan. … The efficacy and usefulness of IDeg and FlexTouch, compared with insulin glargine or detemir, were assessed in patients with type 2 diabetes mellitus. … thereafter, basal insulin was replaced by an IDeg-prefilled FlexTouch with the same dose and duration of time (2 weeks). …
• NAID 130005086447

Related Pictures

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★リンクテーブル★

リンク元	「インスリングラルギン」「インスリングラルジン」

「インスリングラルギン」

　　[★]

英

insulin glargine

商

ランタス

関

インスリングラルジン、その他のホルモン剤

商品名

• インスリングラルギン

会社名

• 日本イーライリリー
• 富士フイルムファーマ

成分

• インスリングラルギン

薬効分類

• 持効型溶解インスリンアナログ製剤

薬効

• インスリン療法が適応となる糖尿病を効能・効果とするバイオ後続品

「インスリングラルジン」

　　[★]

英

insulin glargine

関

インスリングラルギン