Insulin glargine: Difference between revisions

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{{Short description|Long-acting insulin}}

{{Infobox drug

| caption          = Toujeo branded insulin glargine

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| pronounce        =

| biosimilars = insulin glargine-aglr, insulin glargine-yfgn, Rezvoglar, Abasaglar, Semglee

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| legal_AU = S4

| legal_status      = Rx-only

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| bioavailability =

| excretion =

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| CAS_number_Ref = {{cascite|correct|??}}

| synonyms          =  

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| IUPAC_name = Recombinant human insulin

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'''Insulin glargine''' sold under the brand name '''Lantus''' among others is a long-acting [[insulin analogue|modified]] form of [[insulin (medication)|medical insulin]], used in the management of [[type 1 DM|type I]] and [[type II diabetes]]. It is [[subcutaneous injection|injected just under the skin]]. Effects generally begin an hour after use.

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

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Insulin glargine was approved for medical use in the United States in 2000. It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]]. In 2021, it was the 29th most commonly prescribed medication in the United States with more than 19{{nbsp}}million prescriptions. 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.

The long-acting insulin class, which includes insulin glargine, do not appear much better than [[NPH insulin|neutral protamine Hagedorn (NPH) insulin]], but do have a greater cost, making them, as of 2010, not cost effective for the treatment of type 2 diabetes. 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, however a more recent [[Cochrane (organisation)|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. It is not typically the recommended long acting insulin in the United Kingdom.

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

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.

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

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

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.

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. It can achieve a peakless level for at least 24 hours.

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.

On 9 June 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 9 June 2005.

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

=== Legal status ===

==== Biosimilars ====

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

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

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

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

Patent protection for insulin glargine expired in most countries in 2015 and in the U.S.A. is expected to expire on 2027-07-05. Insulin glargine from competitor [[Eli Lilly and Company|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).

{{Oral hypoglycemics and insulin analogs}}

{{Eli Lilly and Company}}

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{{二次利用|date=7 February 2024}}

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