Insulin glargine

Last updated

Insulin glargine
Toujeo 300 IU-ml inj.jpg
Toujeo branded insulin glargine
Clinical data
Trade names Lantus, others
Biosimilars insulin glargine-aglr, insulin glargine-yfgn, Abasaglar, Rezvoglar, Semglee
AHFS/Drugs.com Monograph
MedlinePlus a600027
License data
Pregnancy
category
Routes of
administration 		Subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Onset of action ~1 hour [7]
Duration of action 24–36 hours [7]
Identifiers
  • Recombinant human insulin
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.241.126 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C267H404N72O78S6
Molar mass 6062.96 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 1 and type 2 diabetes. [7] It is injected just under the skin. [7] Effects generally begin an hour after use. [7]

Contents

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 patented, but the patent expired in most jurisdictions in 2014. It 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 2022, it was the 28th most commonly prescribed medication in the United States, with more than 18 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 1 diabetes in either adults or children over 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 its reference product Lantus (insulin glargine), a long-acting insulin analog. [12]

Mixing with other insulins

The American Diabetes Association say that, unlike some other longer-acting insulins, glargine should not be diluted or mixed with other insulin or solution in the same syringe, due to the low pH of its diluent. [16] However, a 2004 study found that mixing glargine with other insulins did not affect short-term glycemic profile. [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 1 diabetes in either adults or children in periods of six 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]

History

In June 2000, the European Commission formally approved the launching of Lantus by Sanofi-Aventis Germany in the 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]

Biosimilars

Abasaglar was approved for medical use in the European Union in September 2014. [25] [26]

Lusduna was approved for medical use in the European Union in January 2017. [27]

In March 2018, insulin glargine (Semglee) was approved for medical use in the European Union. [28]

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. [12]

Patent expiry

Patent protection for insulin glargine expired in Europe and the US in 2014. [29] 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). [29]

Brand names

Insulin glargine is available under brand names including Basaglar, Lantus, and Toujeo.

Related Research Articles

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Filgrastim</span> Medication

Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause. It may also be used to increase white blood cells for gathering during leukapheresis. It is given either by injection into a vein or under the skin. Filgrastim is a leukocyte growth factor.

<span class="mw-page-title-main">Irbesartan</span> Chemical compound

Irbesartan, sold under the brand name Aprovel among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.

Feline diabetes mellitus is a chronic disease in cats whereby either insufficient insulin response or insulin resistance leads to persistently high blood glucose concentrations. Diabetes affects up to 1 in 230 cats, and may be becoming increasingly common. Diabetes is less common in cats than in dogs. The condition is treatable, and if treated properly the cat can experience a normal life expectancy. In cats with type 2 diabetes, prompt effective treatment may lead to diabetic remission, in which the cat no longer needs injected insulin. Untreated, the condition leads to increasingly weak legs in cats and eventually to malnutrition, ketoacidosis and/or dehydration, and death.

An insulin analog is any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of controlling blood glucose levels in diabetes. Through genetic engineering of the underlying DNA, the amino acid sequence of insulin can be changed to alter its ADME characteristics. Officially, the U.S. Food and Drug Administration (FDA) refers to these agents as insulin receptor ligands, although they are usually just referred to as insulin analogs or even just insulin.

<span class="mw-page-title-main">Insulin glulisine</span> Rapid-acting insulin analogue

Insulin glulisine, sold under the brand name Apidra among others, is a rapid-acting modified form of medical insulin used for the treatment of diabetes. It differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. When injected subcutaneously, it appears in the blood earlier than regular human insulin (RHI). Intravenous injections may be used for extreme hyperglycemia. It was developed by Sanofi-Aventis.

Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours.

<span class="mw-page-title-main">Insulin aspart</span> Rapid-acting man-made insulin

Insulin aspart, sold under the brand name NovoLog, among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes. It is generally used by injection under the skin but may also be used by injection into a vein. Maximum effect occurs after about 1–3 hours and lasts for 3–5 hours. Generally a longer-acting insulin like insulin NPH is also needed.

<span class="mw-page-title-main">Insulin lispro</span> Rapid-acting insuline analog

Insulin lispro, sold under the brand name Humalog among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes. It is delivered subcutaneously either by injection or from an insulin pump. Onset of effects typically occurs within 30 minutes and lasts about 5 hours. Often a longer-acting insulin like insulin NPH is also needed.

A biosimilar is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved versions of original "innovator" products and can be manufactured when the original product's patent expires. Reference to the innovator product is an integral component of the approval.

<span class="mw-page-title-main">Liraglutide</span> Anti-diabetic medication

Liraglutide, sold under the brand name Victoza among others, is an anti-diabetic medication used to treat type 2 diabetes, and chronic obesity. It is a second-line therapy for diabetes following first-line therapy with metformin. Its effects on long-term health outcomes like heart disease and life expectancy are unclear. It is given by injection under the skin.

Aflibercept, sold under the brand names Eylea and Zaltrap among others, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals.

<span class="mw-page-title-main">Insulin (medication)</span> Use of insulin protein and analogs as medical treatment

As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. Insulin is also used along with glucose to treat hyperkalemia. Typically it is given by injection under the skin, but some forms may also be used by injection into a vein or muscle. There are various types of insulin, suitable for various time spans. The types are often all called insulin in the broad sense, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. It is on the World Health Organization's List of Essential Medicines. In 2022, it was the 192nd most commonly prescribed medication in the United States, with more than 2 million prescriptions.

Lixisenatide is a once-daily injectable GLP-1 receptor agonist for the treatment of type 2 diabetes.

<span class="mw-page-title-main">Insulin degludec</span> Ultralong-acting basal insulin analogue

Insulin degludec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Tresiba. It is administered via subcutaneous injection to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 42 hours, making it a once-daily basal insulin, that is one that provides a base insulin level, as opposed to the fast- and short-acting bolus insulins.

<span class="mw-page-title-main">Dulaglutide</span> Diabetes medication

Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors.

Insulin degludec/liraglutide, sold under the brand name Xultophy, is a fixed-dose combination medication for the treatment of adults with type 2 diabetes to improve glycemic control in combination with diet and exercise. It contains insulin degludec and liraglutide. It is administered by subcutaneous injection.

Insulin glargine/lixisenatide, sold under the brand name Soliqua among others, is a fixed-dose combination medication that combines insulin glargine and lixisenatide and is used to treat diabetes.

Sotagliflozin, sold under the brand name Inpefa among others, is a medication used to reduce the risk of death due to heart failure. It is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Tirzepatide</span> Anti-diabetic and weight loss medication

Tirzepatide is an antidiabetic medication used for the treatment of type 2 diabetes and for weight loss. Tirzepatide is administered via subcutaneous injections. It is sold under the brand name Mounjaro for diabetes treatment, and Zepbound for weight loss and treatment of obstructive sleep apnea.

References

  1. ↑ "Insulin glargine Use During Pregnancy". Drugs.com. 6 April 2020. Archived from the original on 21 October 2020. Retrieved 4 September 2020.
  2. ↑ "Summary Basis of Decision - Semglee". Health Canada. 23 August 2022. Archived 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). Archived from the original on 9 January 2021. Retrieved 7 May 2020.
  4. ↑ "Lantus- insulin glargine injection, solution Lantus SoloStar- insulin glargine injection, solution". DailyMed. Archived from the original on 29 July 2021. Retrieved 29 July 2021.
  5. ↑ "Lantus EPAR". European Medicines Agency (EMA). 8 May 2009. Archived from the original on 4 August 2020. Retrieved 28 July 2021.
  6. ↑ "Toujeo EPAR". European Medicines Agency (EMA). 11 May 2009. Archived from the original on 29 July 2021. Retrieved 28 July 2021.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 "Insulin Glargine Monograph for Professionals". Drugs.com. AHFS. Archived from the original on 5 December 2020. Retrieved 23 December 2018.
  8. 1 2 British national formulary: BNF 76 (76th ed.). Pharmaceutical Press. 2018. p. 701. ISBN   9780857113382.
  9. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  10. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  11. ↑ "Insulin Glargine Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  12. 1 2 3 4 5 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  13. 1 2 3 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, et al. (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). 8 May 2009. Archived from the original on 4 August 2020. Retrieved 7 May 2020.
  22. ↑ EPAR Lantus Archived 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. Archived from the original on 27 February 2015.
  24. ↑ "Toujeo: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 14 August 2020. Retrieved 7 May 2020.
  25. ↑ "Abasaglar EPAR". European Medicines Agency (EMA). 14 October 2014. Archived from the original on 2 April 2022. Retrieved 28 July 2021.
  26. ↑ "Abasaglar Product information". Union Register of medicinal products. 11 September 2014. Retrieved 1 October 2023.
  27. ↑ "Lusduna EPAR". European Medicines Agency (EMA). 12 January 2017. Archived from the original on 29 July 2021. Retrieved 28 July 2021.
  28. ↑ "Semglee EPAR". European Medicines Agency (EMA). 23 May 2018. Archived from the original on 15 February 2022. Retrieved 28 July 2021.
  29. 1 2 "Biosimilars of insulin glargine". GaBI Generics and Biosimilars Initiative. 27 November 2020.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.