Insulin glargine

from Wikipedia, the free encyclopedia
Insulin glargine
Mass / length primary structure 53 amino acids, 6.06  kDa
Identifier
External IDs
Drug information
ATC code A10 AE04
DrugBank BTD00045
Drug class Antidiabetic drug

Insulin glargine ( Insulinum glarginum ; trade names: Toujeo , Lantus ) is a drug from the group of insulin analogues that is used to treat diabetes (diabetes mellitus) and is one of the basal insulins . The active ingredient is a recombinant protein that is produced from genetically modified microorganisms . It is slightly different from the body's own insulin. Compared to other delayed insulins, it has a longer half-life , which means that it is absorbed more slowly and more evenly by the body after the injection, and enables it to be administered once a day.

Clinical information

Insulin glargine is approved as a finished medicinal product for the treatment of type 1 and type 2 diabetes mellitus in adults and, to a limited extent, in children from 6 years of age. As a rule, it is injected subcutaneously once a day or, if it is not effective for 24 hours, twice a day and always at the same time each day. To date, neither clinical nor epidemiological data are available on the risks of use during pregnancy or breastfeeding . Like other medications, insulin glargine must not be used if you are hypersensitive or allergic to the active ingredient.

As adverse effects reactions occur at the injection site. As with any insulin therapy, changes in the subcutaneous fat tissue ( lipodystrophy ), buildup (hypertrophy) of the subcutaneous fat tissue ( lipohypertrophy ) and, to a lesser extent, fat depletion ( lipoatrophy ) can occur at the injection site . In rare cases there are allergic reactions, taste disturbances , visual disturbances with significant changes in the blood sugar control. Continuously improving blood sugar control reduces the risk of developing an eye disease caused by diabetes ( diabetic retinopathy ). However, with intensified insulin therapy or an abrupt improvement in blood sugar levels induced by insulin glargine, diabetic retinopathy can temporarily worsen. Muscle pain and edema are very rare . Hypoglycaemia, which is a very common side effect of insulin therapy, can occur if the insulin dose exceeds the requirement.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Insulin glargine works by binding to the insulin receptors and primarily causes the lowering of the blood glucose level .

It binds to the IGF-1 receptor more strongly than human insulin .

Absorption and distribution in the body (pharmacokinetics)

The finished medicinal product is formulated as an acidic solution with a pH of 4 in which the active ingredient is dissolved. After injection , the acidic solution in the subcutaneous tissue ( subcutis ) is slowly neutralized , with insulin glargine microcrystals being formed. These slowly dissolve and enter the bloodstream as a biologically active form . With daily administration, a steady state is established after two to four days, i.e. a stable plasma level without fluctuations.

Other Information

Chemical and pharmaceutical information

In the amino acid sequence compared to human insulin, insulin glargine has the amino acid glycine at position A21 (Asn21) instead of asparagine . The B chain is extended by two arginine units. 

Insulin glargin
          ┌─────────┐
G-I-V-E-Q-C-C-T-S-I-C-S-L-Y-Q-L-E-N-Y-C-G
            │                       ┌─┘
F-V-N-Q-H-L-C-G-S-H-L-V-E-A-L-Y-L-V-C-G-E-R-G-F-F-Y-T-P-K-T-R-R

Insulin glargine is formulated in the product Lantus (manufactured for the first time by Sanofi-Aventis ) and in the biosimilar Abasaglar together with zinc , m- cresol as well as sodium hydroxide and hydrochloric acid as inactive ingredients . It is offered in 3 ml cylindrical ampoules for use in insulin pens or 10 ml bottles.

Since 2015, insulin glargine has also been available as insulin glargine U300 with 300 U / ml (trade name Toujeo ) and as the first insulin biosimilar (trade name Abasaglar ), since 2017 as another insulin biosimilar (trade name Lusduna ).

development

On June 9, 2000, the European Commission granted the pharmaceutical company Sanofi-Aventis Deutschland GmbH a license to market Lantus throughout the European Union .

Abasaglar from the manufacturer Lilly and Boehringer Ingelheim has been available since September 1, 2015, and Lusduna from the manufacturer MSD Sharp & Dohme since January 2017 .

Studies

In a comprehensive analysis of the existing studies on insulin glargine in 2009, IQWiG found no advantages in the treatment of type 2 diabetes mellitus for blood sugar control, mortality , retinopathies and the number of hospital treatments compared to NPH insulin . However, with insulin glargine a statistically significant advantage with regard to severe hypoglycaemia compared to NPH insulin is seen. This advantage of increased safety against hypoglycaemia is also confirmed for insulin glargine by other systematic reviews .

The question of whether the use of insulin glargine can promote the growth of cancer cells is controversial . A very extensive study carried out in Germany in 2009 came to the conclusion that the use of insulin glargine may increase the risk of cancer compared to patients treated with human insulin. The authors admitted, however, that this question could not be conclusively assessed on the basis of the documents available to them; further long-term studies are required. There was no differentiation between the types of diabetes or with regard to influencing factors such as previous illnesses, body weight, general cancer risk, previous cancer diseases or the duration of the diabetes illness. A study published at the same time that was carried out in Scotland found no increased cancer risk in diabetics treated with insulin glargine that could be attributed to the use of insulin glargine. At the congress of the German Diabetes Society in 2012, a meta-study was presented according to which no connection between insulin glargine and the cancer risk could be demonstrated. The cancer risk in patients treated with insulin glargine is even slightly lower than in general. In conclusion, however, because of the latency in the development of tumors, this can only be assessed after a period of ten to 30 years after the drug was launched.

Germany

According to the resolution of the Federal Joint Committee (G-BA) of March 18, 2010, the active ingredient insulin glargine or the preparation Lantus for the treatment of type 2 diabetes cannot be prescribed "as long as it - taking into account the necessary dosages to achieve the therapeutic goal - There are additional costs associated with intermediate-acting human insulin (NPH). (...) For the determination of the additional costs, the actual costs incurred by the responsible health insurance company are decisive. ". The real price difference between Lantus and conventional delay insulin is said to be 19 cents per day, according to a study; This is completely offset by cost savings in contrast to short-acting insulins, for example with test strips, so that cost neutrality is created.

According to the new resolution in Germany, SHI patients with type 2 diabetes whose health insurance companies have not signed a contract with Sanofi-Aventis and who are already receiving a long-acting insulin analog should switch to NPH insulin and those who are receiving insulin therapy for the first time should also be adjusted to NPH insulin, but this prescription restriction does not apply to patients who, after appropriate testing, are at high risk of severe hypoglycaemia ; it also does not apply to those rare cases where there may be an allergic reaction to intermediate human insulins. The rule according to which reimbursement remains in place in the event of a severe risk of hypoglycaemia only applies to Lantus. The reason for this special feature of Lantus is the final report of the IQWiG, which recognizes an advantage for Lantus over NPH insulin with regard to a lower risk of severe hypoglycaemia.

The G-BA resolution, which came into force on July 14, 2010, states that Lantus will also remain fully reimbursable in the future for all those insured by statutory health insurance companies who have concluded value-added contracts with Sanofi-Aventis (Sanofi-Aventis offers the health insurers a contractual Guarantee to make up for a difference in costs). According to its own information, Sanofi-Aventis has already concluded such contracts with around 95% of the health insurance companies, so that insulin glargine can still be prescribed for most patients.

United States

The longer-acting insulins such as insulin glargine are just as effective as NPH insulin , but more expensive. Long-term results are not yet available. In contrast to other longer-acting insulins, insulin glargine must not be mixed with other insulins in a syringe. This practice has been challenged in clinical studies.

literature

  • EPAR Lantus. (PDF; 66 kB) - Summary of the European public assessment report for Lantus (German)

Web links

Individual evidence

  1. ↑ Hellmut Mehnert: Diabetology in clinic and practice. Thieme, Stuttgart May 2003, 5th edition, p. 257, ISBN 978-3-13-512805-4 .
  2. ↑ E. Mutschler, G. Geisslinger, HK Kroemer, S. Menzel, P. Ruth: Mutschler drug effects. Pharmacology - Clinical Pharmacology - Toxicology. 10th edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2012, ISBN 3-8047-2898-7 , p. 385.
  3. ↑ Peter Hürter: Diabetes in Children and Adolescents. Springer-Verlag, 2013, ISBN 978-3-662-06575-4 , p. 134 ( limited preview in the Google book search).
  4. ↑ EPAR Lantus (PDF; 66 kB) German summary of the approval report of the European Medicines Agency .
  5. ^ EPAR: Summary of the EPAR for the public. (PDF) EPAR, accessed December 12, 2016 .
  6. ↑ Final report A0503 (PDF) from IQWiG on long-acting insulin analogues in type 2 diabetes mellitus (PDF).
  7. ^ SR Singh, F Ahmad, A Lal, C Yu, Z Bai, H Bennett: Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis . In: | CMAJ . Volume 180, No. 4, February 2009, pp. 385-397, PMID 19221352 , PMC 2638025 (free full text), doi: 10.1503 / cmaj.081041
  8. ↑ Harro Albrecht: Insulin shock. The analog insulin Lantus, injected millions of times, is suspected of stimulating the growth of cancer cells . In: Die Zeit , No. 28 / 2009-
  9. ↑ LG Hemkens, U. Grouven, R. Bender, C. Günster, S. Gutschmidt, GW Selke, PT Sawicki: Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. In: Diabetologia. 52, 2009, pp. 1732–1744, doi: 10.1007 / s00125-009-1418-4 : One major limitation of the study is the fact that patients were not randomized to treatment groups. Although the results were adjusted for all known and available confounders, potentially relevant factors such as insulin resistance, body mass index, smoking, social status and duration of diabetes were not available and therefore could not be considered in the analyzes. However, to explain the observed dose-dependent risk increase in the glargine group, these potential confounders would have to be associated with both a higher cancer risk and a higher glargine dosage. For example, we have no evidence that the glargine group included more smokers or people from a lower socioeconomic class; In fact, at baseline, the glargine group generally seemed to be healthier than the human insulin group, and these findings were consistent when comparing subgroups of patients within the same dose range (p. 1738f.)
  10. ↑ HM Colhoun: Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. In: Diabetologia. 52, 2009, pp. 1755-1765, doi: 10.1007 / s00125-009-1453-1 .
  11. ↑ Sven Siebenand: Type 2 diabetes and cancer. Not a one-way street. In: Pharmaceutical newspaper online. Retrieved on June 25, 2012 (article in No. 21/2012).
  12. ^ G-BA decision. In: Bundesanzeiger , issue No. 103 of July 14, 2010, p. 2422, g-ba.de (PDF; 287 kB)
  13. ↑ Thieme Health Economics Report 2010 , 1. pp. 1–46.
  14. ↑ G-BA: Medicines Directive / Annex III (long-acting insulin analogues for the treatment of type 2 diabetes mellitus) .
  15. ↑ Long-acting insulin analogues . (PDF) iqwig.de
  16. ↑ List of health insurance companies with discount / value-added contracts .
  17. ↑ G-BA resolution on insulin analogues: Unjustified drug costs no longer charged to the statutory health insurance. Press release. Federal Joint Committee, March 18, 2010, accessed on October 21, 2016 .
  18. ↑ Deutsche Apotherkerzeitung from July 2, 2010 online ( Memento from July 8, 2010 in the Internet Archive ).
  19. ↑ German Medical Journal, July 11, 2010 online .
  20. ^ N Waugh, E Cummins, P Royle, C Clar, M Marien, B Richter, S Philip: Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation . In: Health technology assessment (Winchester, England) , July 2010, Volume 14, No. 36, pp. 1-248, PMID 20646668 , doi: 10.3310 / hta14360
  21. ^ SR Singh, F Ahmad, A Lal, C Yu, Z Bai, H Bennett: Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis . In: CMAJ , Volume 180, No. 4, February 2009, pp. 385-397, PMID 19221352 , PMC 2638025 (free full text), doi: 10.1503 / cmaj.081041
  22. ^ American Diabetes Association: Position statement: Insulin administration . In: Diabetes Care . 26, No. Suppl. 1, 2003, pp. 121-124.
  23. ^ W. Kaplan et al .: Effects of Mixing Glargine and Short-Acting Insulin Analogs on Glucose Control . In: Diabetes Care , 2004, Volume 27, No. 11, pp. 2739-2740, PMID 15505016 , doi: 10.2337 / diacare.27.11.2739