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Insulin glargine

August 22, 2023

Insulin glargine sold under the brand name Lantus among others is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes.[7] It is injected just under the skin.[7] Effects generally begin an hour after use.[7]

Insulin glargine
Toujeo branded insulin glargine
Clinical data
Trade namesLantus, Toujeo, Basaglar, others
Biosimilarsinsulin glargine-aglr, insulin glargine-yfgn, Rezvoglar, Abasaglar, Semglee
AHFS/Drugs.comMonograph
MedlinePlusa600027
License data
Pregnancy
category
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Onset of action~1 hours[7]
Duration of action24 to 36 hours[7]
Identifiers
  • Recombinant human insulin
CAS Number
  • 160337-95-1 Y
IUPHAR/BPS
  • 7572
DrugBank
  • DB00047 Y
ChemSpider
  • none
UNII
  • 2ZM8CX04RZ
KEGG
  • D03250 Y
CompTox Dashboard (EPA)
  • DTXSID0043927
ECHA InfoCard100.241.126
Chemical and physical data
FormulaC267H404N72O78S6
Molar mass6062.96 g·mol−1
 NY (what is this?)  (verify)

Common side effects include low blood sugar, problems at the site of injection, itchiness, and weight gain.[7] Other serious side effects include low blood potassium.[7] NPH insulin rather than insulin glargine is generally preferred in pregnancy.[8] After injection, microcrystals slowly release insulin for about 24 hours.[7] This insulin causes body tissues to absorb glucose from the blood and decreases glucose production by the liver.[7]

Insulin glargine was approved for medical use in the United States in 2000.[7] It is on the World Health Organization's List of Essential Medicines.[9] In 2020, it was the 32nd most commonly prescribed medication in the United States with more than 17 million prescriptions.[10][11] In July 2021, the US Food and Drug Administration (FDA) approved an interchangeable biosimilar insulin product called Semglee (insulin glargine-yfgn) for the treatment of diabetes.[12]

Medical uses

The long-acting insulin class, which includes insulin glargine, do not appear much better than neutral protamine Hagedorn (NPH) insulin,[13] but do have a greater cost, making them, as of 2010, not cost effective for the treatment of type 2 diabetes.[14] In a previous review it was unclear if there is a difference in hypoglycemia, as there was not enough data to determine any differences with respect to long term outcomes,[15] however a more recent Cochrane systematic review did not find clinically significant difference when comparing insulin glargine to NPH insulin, insulin detemir or insulin degludec in the management of type I Diabetes in neither adults or children in periods of 6 months or longer.[13] It is not typically the recommended long acting insulin in the United Kingdom.[8]

Semglee is indicated to improve glycemic control in adults and children with Type 1 diabetes and in adults with Type 2 diabetes.[12] Semglee is both biosimilar to, and interchangeable with (can be substituted for), its reference product Lantus (insulin glargine), a long-acting insulin analog.[12]

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.[16] However, this restriction has been questioned.[17]

Adverse effects

Common side effects include low blood sugar, problems at the site of injection, itchiness, and weight gain.[7] Serious side effects include low blood potassium.[7]

As of 2012, tentative evidence shows no association between insulin glargine and cancer.[18] Previous studies had raised concerns.[19]

When comparing insulin glargine to NPH insulin, insulin detemir or insulin degludec, no significant adverse effects were found in the management of type I Diabetes in neither adults or children in periods of 6 months or longer.[13]

Pharmacology

Mechanism of action

Insulin glargine differs from human insulin by replacing asparagine with glycine in position 21 of the A-chain and by carboxy-terminal extension of B-chain by 2 arginine residues. The arginine amino acids shift 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.[20] 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

On 9 June 2000, the European Commission formally approved the launching of Lantus by Sanofi-Aventis Germany Ltd. in the entire European Union.[21] The admission was prolonged on 9 June 2005.[22]

A three-fold more concentrated formulation, brand name Toujeo, was introduced after FDA approval in 2015.[23][24]

Society and culture

Legal status

Biosimilars

Abasaglar was approved for medical use in the European Union in September 2014.[25]

Lusduna was approved for medical use in the European Union in January 2017.[26]

In March 2018, insulin glargine (Semglee) was approved for medical use in the European Union.[27]

In July 2021, insulin glargine-yfgn (Semglee) was approved for medical use in the United States as the first interchangeable biosimilar of Lantus.[12] The FDA granted approval of Semglee to Mylan Pharmaceuticals Inc.[12]

Patent expiry

Patent protection for insulin glargine expired in most countries in 2015[citation needed] and in the U.S.A. is expected to expire on 2027-07-05.[28] Insulin glargine from competitor Eli Lilly became available in most countries during 2015, under the brand names Basaglar (as a follow-on in the US) and Abasaglar (as a biosimilar in the EU).[citation needed]

References

  1. ^ "Insulin glargine Use During Pregnancy". Drugs.com. 6 April 2020. from the original on 21 October 2020. Retrieved 4 September 2020.
  2. ^ "Summary Basis of Decision - Semglee". Health Canada. 23 August 2022. from the original on 29 September 2022. Retrieved 29 September 2022.
  3. ^ "Lantus 100 units/ml solution for injection in a cartridge - Summary of Product Characteristics (SmPC)". (emc). from the original on 9 January 2021. Retrieved 7 May 2020.
  4. ^ "Lantus- insulin glargine injection, solution Lantus SoloStar- insulin glargine injection, solution". DailyMed. from the original on 29 July 2021. Retrieved 29 July 2021.
  5. ^ "Lantus EPAR". European Medicines Agency (EMA). 17 September 2018. from the original on 4 August 2020. Retrieved 28 July 2021.
  6. ^ "Toujeo EPAR". European Medicines Agency (EMA). 17 September 2018. from the original on 29 July 2021. Retrieved 28 July 2021.
  7. ^ a b c d e f g h i j k l "Insulin Glargine Monograph for Professionals". Drugs.com. AHFS. from the original on 5 December 2020. Retrieved 23 December 2018.
  8. ^ a b British national formulary: BNF 76 (76th ed.). Pharmaceutical Press. 2018. p. 701. ISBN 9780857113382.
  9. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  10. ^ "The Top 300 of 2020". ClinCalc. from the original on 12 February 2021. Retrieved 7 October 2022.
  11. ^ "Insulin Glargine - Drug Usage Statistics". ClinCalc. from the original on 29 November 2020. Retrieved 7 October 2022.
  12. ^ a b c d e "FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes". U.S. Food and Drug Administration (FDA) (Press release). 28 July 2021. from the original on 28 August 2021. Retrieved 28 July 2021.   This article incorporates text from this source, which is in the public domain.
  13. ^ a b c Hemmingsen B, Metzendorf MI, Richter B (March 2021). "(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus". The Cochrane Database of Systematic Reviews. 3 (4): CD013498. doi:10.1002/14651858.cd013498.pub2. PMC 8094220. PMID 33662147.
  14. ^ Waugh N, Cummins E, Royle P, Clar C, Marien M, Richter B, Philip S (July 2010). "Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation". Health Technology Assessment. 14 (36): 1–248. doi:10.3310/hta14360. PMID 20646668.
  15. ^ Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H (February 2009). "Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis". CMAJ. 180 (4): 385–397. doi:10.1503/cmaj.081041. PMC 2638025. PMID 19221352.
  16. ^ American Diabetes Association (January 2003). "Insulin administration". Diabetes Care. 26 (Suppl. 1): S121–S124. doi:10.2337/diacare.26.2007.S121. PMID 12502637.
  17. ^ Kaplan W, Rodriguez LM, Smith OE, Haymond MW, Heptulla RA (November 2004). "Effects of mixing glargine and short-acting insulin analogs on glucose control". Diabetes Care. 27 (11): 2739–2740. doi:10.2337/diacare.27.11.2739. PMID 15505016.
  18. ^ Tang X, Yang L, He Z, Liu J (2012). "Insulin glargine and cancer risk in patients with diabetes: a meta-analysis". PLOS ONE. 7 (12): e51814. Bibcode:2012PLoSO...751814T. doi:10.1371/journal.pone.0051814. PMC 3526637. PMID 23284776.
  19. ^ Rendell M, Akturk HK, Tella SH (March 2013). "Glargine safety, diabetes and cancer". Expert Opinion on Drug Safety. 12 (2): 247–263. doi:10.1517/14740338.2013.770469. PMID 23394441. S2CID 9224923.
  20. ^ Bolli GB, Di Marchi RD, Park GD, Pramming S, Koivisto VA (October 1999). "Insulin analogues and their potential in the management of diabetes mellitus". Diabetologia. 42 (10): 1151–1167. doi:10.1007/s001250051286. PMID 10525654.
  21. ^ "Lantus EPAR". European Medicines Agency (EMA). 17 September 2018. from the original on 4 August 2020. Retrieved 7 May 2020.
  22. ^ EPAR Lantus 22 November 2006 at the Wayback Machine, German summary of admission report of the European Medicines Agency (PDF)
  23. ^ "Sanofi Receives FDA Approval of Once-Daily Basal Insulin Toujeo" (Press release). Sanofi. 25 February 2015. from the original on 27 February 2015.
  24. ^ "Toujeo: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). from the original on 14 August 2020. Retrieved 7 May 2020.
  25. ^ "Abasaglar EPAR". European Medicines Agency (EMA). 17 September 2018. from the original on 2 April 2022. Retrieved 28 July 2021.
  26. ^ "Lusduna EPAR". European Medicines Agency (EMA). 17 September 2018. from the original on 29 July 2021. Retrieved 28 July 2021.
  27. ^ "Semglee EPAR". European Medicines Agency (EMA). 17 September 2018. from the original on 15 February 2022. Retrieved 28 July 2021.
  28. ^ "Amidated insulin glargine". from the original on 29 September 2022. Retrieved 17 August 2020.

External links

  • "Insulin glargine". Drug Information Portal. U.S. National Library of Medicine.

August 22, 2023
insulin, glargine, sold, under, brand, name, lantus, among, others, long, acting, modified, form, medical, insulin, used, management, type, type, diabetes, injected, just, under, skin, effects, generally, begin, hour, after, toujeo, branded, insulin, glarginec. Insulin glargine sold under the brand name Lantus among others is a long acting modified form of medical insulin used in the management of type I and type II diabetes 7 It is injected just under the skin 7 Effects generally begin an hour after use 7 Insulin glargineToujeo branded insulin glargineClinical dataTrade namesLantus Toujeo Basaglar othersBiosimilarsinsulin glargine aglr insulin glargine yfgn Rezvoglar Abasaglar SemgleeAHFS Drugs comMonographMedlinePlusa600027License dataEU EMA by INN US DailyMed Insulin glarginePregnancycategoryAU B3 1 Routes ofadministrationSubcutaneousATC codeA10AE04 WHO Legal statusLegal statusAU S4 Prescription only CA only Schedule D 2 UK POM Prescription only 3 US only 4 EU Rx only 5 6 In general Prescription only Pharmacokinetic dataOnset of action 1 hours 7 Duration of action24 to 36 hours 7 IdentifiersIUPAC name Recombinant human insulinCAS Number160337 95 1 YIUPHAR BPS7572DrugBankDB00047 YChemSpidernoneUNII2ZM8CX04RZKEGGD03250 YCompTox Dashboard EPA DTXSID0043927ECHA InfoCard100 241 126Chemical and physical dataFormulaC 267H 404N 72O 78S 6Molar mass6062 96 g mol 1 N Y what is this verify Common side effects include low blood sugar problems at the site of injection itchiness and weight gain 7 Other serious side effects include low blood potassium 7 NPH insulin rather than insulin glargine is generally preferred in pregnancy 8 After injection microcrystals slowly release insulin for about 24 hours 7 This insulin causes body tissues to absorb glucose from the blood and decreases glucose production by the liver 7 Insulin glargine was approved for medical use in the United States in 2000 7 It is on the World Health Organization s List of Essential Medicines 9 In 2020 it was the 32nd most commonly prescribed medication in the United States with more than 17 million prescriptions 10 11 In July 2021 the US Food and Drug Administration FDA approved an interchangeable biosimilar insulin product called Semglee insulin glargine yfgn for the treatment of diabetes 12 Contents 1 Medical uses 1 1 Mixing with other insulins 2 Adverse effects 3 Pharmacology 3 1 Mechanism of action 3 2 Acceptance and repartition in the body 4 History 5 Society and culture 5 1 Legal status 5 1 1 Biosimilars 5 1 2 Patent expiry 6 References 7 External linksMedical uses EditParts of this article those related to documentation need to be updated Please help update this article to reflect recent events or newly available information January 2022 The long acting insulin class which includes insulin glargine do not appear much better than neutral protamine Hagedorn NPH insulin 13 but do have a greater cost making them as of 2010 not cost effective for the treatment of type 2 diabetes 14 In a previous review it was unclear if there is a difference in hypoglycemia as there was not enough data to determine any differences with respect to long term outcomes 15 however a more recent Cochrane systematic review did not find clinically significant difference when comparing insulin glargine to NPH insulin insulin detemir or insulin degludec in the management of type I Diabetes in neither adults or children in periods of 6 months or longer 13 It is not typically the recommended long acting insulin in the United Kingdom 8 Semglee is indicated to improve glycemic control in adults and children with Type 1 diabetes and in adults with Type 2 diabetes 12 Semglee is both biosimilar to and interchangeable with can be substituted for its reference product Lantus insulin glargine a long acting insulin analog 12 Mixing with other insulins Edit Unlike some other longer acting insulins glargine must not be diluted or mixed with other insulin or solution in the same syringe 16 However this restriction has been questioned 17 Adverse effects EditCommon side effects include low blood sugar problems at the site of injection itchiness and weight gain 7 Serious side effects include low blood potassium 7 As of 2012 tentative evidence shows no association between insulin glargine and cancer 18 Previous studies had raised concerns 19 When comparing insulin glargine to NPH insulin insulin detemir or insulin degludec no significant adverse effects were found in the management of type I Diabetes in neither adults or children in periods of 6 months or longer 13 Pharmacology EditMechanism of action Edit Insulin glargine differs from human insulin by replacing asparagine with glycine in position 21 of the A chain and by carboxy terminal extension of B chain by 2 arginine residues The arginine amino acids shift 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 20 It can achieve a peakless level for at least 24 hours Acceptance and repartition in the body Edit 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 EditOn 9 June 2000 the European Commission formally approved the launching of Lantus by Sanofi Aventis Germany Ltd in the entire European Union 21 The admission was prolonged on 9 June 2005 22 A three fold more concentrated formulation brand name Toujeo was introduced after FDA approval in 2015 23 24 Society and culture EditLegal status Edit Biosimilars Edit Abasaglar was approved for medical use in the European Union in September 2014 25 Lusduna was approved for medical use in the European Union in January 2017 26 In March 2018 insulin glargine Semglee was approved for medical use in the European Union 27 In July 2021 insulin glargine yfgn Semglee was approved for medical use in the United States as the first interchangeable biosimilar of Lantus 12 The FDA granted approval of Semglee to Mylan Pharmaceuticals Inc 12 Patent expiry Edit Patent protection for insulin glargine expired in most countries in 2015 citation needed and in the U S A is expected to expire on 2027 07 05 28 Insulin glargine from competitor Eli Lilly became available in most countries during 2015 under the brand names Basaglar as a follow on in the US and Abasaglar as a biosimilar in the EU citation needed References Edit Insulin glargine Use During Pregnancy Drugs com 6 April 2020 Archived from the original on 21 October 2020 Retrieved 4 September 2020 Summary Basis of Decision Semglee Health Canada 23 August 2022 Archived from the original on 29 September 2022 Retrieved 29 September 2022 Lantus 100 units ml solution for injection in a cartridge Summary of Product Characteristics SmPC emc Archived from the original on 9 January 2021 Retrieved 7 May 2020 Lantus insulin glargine injection solution Lantus SoloStar insulin glargine injection solution DailyMed Archived from the original on 29 July 2021 Retrieved 29 July 2021 Lantus EPAR European Medicines Agency EMA 17 September 2018 Archived from the original on 4 August 2020 Retrieved 28 July 2021 Toujeo EPAR European Medicines Agency EMA 17 September 2018 Archived from the original on 29 July 2021 Retrieved 28 July 2021 a b c d e f g h i j k l Insulin Glargine Monograph for Professionals Drugs com AHFS Archived from the original on 5 December 2020 Retrieved 23 December 2018 a b British national formulary BNF 76 76th ed Pharmaceutical Press 2018 p 701 ISBN 9780857113382 World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 The Top 300 of 2020 ClinCalc Archived from the original on 12 February 2021 Retrieved 7 October 2022 Insulin Glargine Drug Usage Statistics ClinCalc Archived from the original on 29 November 2020 Retrieved 7 October 2022 a b c d e FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes U S Food and Drug Administration FDA Press release 28 July 2021 Archived from the original on 28 August 2021 Retrieved 28 July 2021 This article incorporates text from this source which is in the public domain a b c Hemmingsen B Metzendorf MI Richter B March 2021 Ultra long acting insulin analogues for people with type 1 diabetes mellitus The Cochrane Database of Systematic Reviews 3 4 CD013498 doi 10 1002 14651858 cd013498 pub2 PMC 8094220 PMID 33662147 Waugh N Cummins E Royle P Clar C Marien M Richter B Philip S July 2010 Newer agents for blood glucose control in type 2 diabetes systematic review and economic evaluation Health Technology Assessment 14 36 1 248 doi 10 3310 hta14360 PMID 20646668 Singh SR Ahmad F Lal A Yu C Bai Z Bennett H February 2009 Efficacy and safety of insulin analogues for the management of diabetes mellitus a meta analysis CMAJ 180 4 385 397 doi 10 1503 cmaj 081041 PMC 2638025 PMID 19221352 American Diabetes Association January 2003 Insulin administration Diabetes Care 26 Suppl 1 S121 S124 doi 10 2337 diacare 26 2007 S121 PMID 12502637 Kaplan W Rodriguez LM Smith OE Haymond MW Heptulla RA November 2004 Effects of mixing glargine and short acting insulin analogs on glucose control Diabetes Care 27 11 2739 2740 doi 10 2337 diacare 27 11 2739 PMID 15505016 Tang X Yang L He Z Liu J 2012 Insulin glargine and cancer risk in patients with diabetes a meta analysis PLOS ONE 7 12 e51814 Bibcode 2012PLoSO 751814T doi 10 1371 journal pone 0051814 PMC 3526637 PMID 23284776 Rendell M Akturk HK Tella SH March 2013 Glargine safety diabetes and cancer Expert Opinion on Drug Safety 12 2 247 263 doi 10 1517 14740338 2013 770469 PMID 23394441 S2CID 9224923 Bolli GB Di Marchi RD Park GD Pramming S Koivisto VA October 1999 Insulin analogues and their potential in the management of diabetes mellitus Diabetologia 42 10 1151 1167 doi 10 1007 s001250051286 PMID 10525654 Lantus EPAR European Medicines Agency EMA 17 September 2018 Archived from the original on 4 August 2020 Retrieved 7 May 2020 EPAR Lantus Archived 22 November 2006 at the Wayback Machine German summary of admission report of the European Medicines Agency PDF Sanofi Receives FDA Approval of Once Daily Basal Insulin Toujeo Press release Sanofi 25 February 2015 Archived from the original on 27 February 2015 Toujeo FDA Approved Drugs U S Food and Drug Administration FDA Archived from the original on 14 August 2020 Retrieved 7 May 2020 Abasaglar EPAR European Medicines Agency EMA 17 September 2018 Archived from the original on 2 April 2022 Retrieved 28 July 2021 Lusduna EPAR European Medicines Agency EMA 17 September 2018 Archived from the original on 29 July 2021 Retrieved 28 July 2021 Semglee EPAR European Medicines Agency EMA 17 September 2018 Archived from the original on 15 February 2022 Retrieved 28 July 2021 Amidated insulin glargine Archived from the original on 29 September 2022 Retrieved 17 August 2020 External links Edit Insulin glargine Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Insulin glargine amp oldid 1164764159, wikipedia, wiki, book, books, library,

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