|Systematic (IUPAC) name|
Recombinant human insulin
|Trade names||Lantus, Toujeo|
|CAS Registry Number|
|Molecular mass||6063 g/mol|
|(what is this?)|
Insulin glargine, marketed under the names Lantus, Toujeo, Abasaglar, and Basaglar 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.
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
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.
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 protection for Lantus expired in February 2015. Generic copies are expected to appear shortly. Back in February 2014 Merck & Co. announced that its version of glargine will soon enter late-stage clinical trials. Eli Lilly and Company also has a generic equivalent in the works, as at February 2014. Eli Lilly's biosimilar glargine known as Abasaglar (formerly Abasria) in the EU, Basaglar (US) and LY2963016 was approved in the EU in September 2014 but the launch has been delayed pending clarification of patent status, following claims of patent infringement in the US.
Toujeo, having only been launched in April 2015, remains under patent.
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- Insulin glargine - MedlinePlus
- Lantus website (Sanofi-Aventis)
- U.S. National Library of Medicine: Drug Information Portal - Insulin glargine
- Comparing Insulins Detemir and Glargine in Type 2 Diabetes: More Similarities than Differences