インスリングラルギン
Insulin glargine/ja
ランタスなどの商品名で販売されているインスリングラルギンは、医療用インスリンの長時間作用型改良型であり、Ⅰ型糖尿病および2型糖尿病の管理に用いられる。皮膚のすぐ下に注射する。効果は一般に使用後1時間で始まる。
 Toujeoブランドのインスリングラルギン | |
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| Trade names | Lantus, Toujeo, Basaglar, others |
| Biosimilars | insulin glargine-aglr, insulin glargine-yfgn, Rezvoglar, Abasaglar, Semglee |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a600027 |
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| Routes of administration | 皮下 |
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| Pharmacokinetic data | |
| Onset of action | ~1 hours |
| Duration of action | 24から36時間 |
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| Formula | C267H404N72O78S6 |
| Molar mass | 6062.96 g·mol−1 |
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一般的な副作用には、低血糖、注射部位の問題、かゆみ、体重増加などがある。その他の重篤な副作用には低血中カリウムがある。インスリングラルギンよりもむしろNPHインスリンが一般的に妊婦で好まれる。注射後、微結晶は約24時間ゆっくりとインスリンを放出する。このインスリンは体組織に血液からグルコースを吸収させ、肝臓によるグルコース産生を減少させる。
インスリングラルギンは、2000年に米国で医薬品として承認された。世界保健機関の必須医薬品リストに掲載されている。2021年には、19 万件以上の処方で、米国で29番目に多く処方されている医薬品であった。2021年7月、米国食品医薬品局（FDA）は、糖尿病治療用のセムグリー（インスリングラルギン-yfgn）と呼ばれる互換性のあるバイオシミラーインスリン製剤を承認した。
Medical uses
The long-acting insulin class, which includes insulin glargine, do not appear much better than 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 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.
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
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.
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. 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. The admission was prolonged on 9 June 2005.
A three-fold more concentrated formulation, brand name Toujeo, was introduced after FDA approval in 2015.
Society and culture
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.
特許失効
インスリングラルギンの特許は2015年にほとんどの国で失効し、米国では2027-07-05に失効する見込みである。競合薬であるEli Lillyのインスリングラルギンは、バサグラー（米国では後続品）、アバサグラー（EUではバイオシミラー）という商品名で、2015年中にほとんどの国で入手可能となった。
