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Revision as of 10:02, 31 October 2011 by Beetstra (talk | contribs) (Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'UNII').)(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff) Pharmaceutical compound| Clinical data | |
|---|---|
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a600027 |
| Routes of administration | Subcutaneous |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| DrugBank | |
| ChemSpider | |
| KEGG | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.241.126  |
| Chemical and physical data | |
| Formula | C267H404N72O78S6 |
| Molar mass | 6063 g/mol g·mol |
Insulin glargine, marketed by Sanofi-Aventis under the name Lantus, 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 Lantus 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 two (in some cases) or latent autoimmune diabetes of adults in late stage—Lantus needs the support of fast acting insulin taken with food to reduce the effect of prandially derived glucose.
Benefit
When standard NPH is administered at night, its peak of action can coincide with the lower serum glucose levels associated with nocturnal metabolism potentially setting the stage for nocturnal hypoglycaemia. Lantus is associated with a lower risk of nocturnal hypoglycaemia.
Pharmacological specifications
Mechanism of action (pharmacodynamics)
Insulin glargine have substitution of glycine for asparagine at A21 and two arginines added to the carboxy terminal of B chain. This allows insulin glargine to form a precipitate (hexamer) when injected subcutaneously into the patient. It can achieve a peakless level for at least 24 hours.
Acceptance and repartition in the body (pharmacokinetic)
Lantus 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 and can be mitigated with the use of the I-port ), 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 microcrystals (called insulin hexamers) which then dissociate into insulin monomers, the functional and physiologically active unit of insulin. This gradual process ensures that small amounts of Lantus are released into the body continuously, giving an almost peakless profile.
Usage
Mixing with other insulin preparations
Unlike some other longer-acting insulins, Lantus must not be diluted or mixed with other insulin or solution in the same syringe.
Other information
Development
The development of Lantus 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 Mio. diabetics applied this preparation. In 2007 Lantus ranked place 15 on top-selling pharmaceutical products in Germany.
The investment in the production of Lantus and insulin-pen-manufacturing at the location Frankfurt-Höchst lied at 700 Mio. €. In 2008 a new manufacturing plant was established for further insulin-pen with an investment sum of 150 Mio. €. At Sanofi-Aventis the production of Lantus created 3000 jobs in Berlin and Frankfurt-Höchst.
On June 9, 2000 the European Commission approbated Sanofi-Aventis Germany Ltd. the launching of Lantus in the entire European Union. The admission was prolonged on June 9, 2005.
Advantages
International clinical studies have confirmed the advantages of insulin glargine in the treatment of heavy hypoglycaemia compared to standard NPH insulin. Insulin glargine reduces the risk of severe nocturnal hypoglycaemia. Extensive clinical studies (ACCORD) have confirmed the higher risk of mortality with higher incidence of severe hypoglycaemia. A comparison trial of insulin detemir and glargine proved that subjects randomized to detemir used slightly higher daily insulin doses, but gained less weight on average than glargine-treated subjects. Other systematic reviews corroborate the results of benefit of insulin glargine regarding lower incidence of severe hypoglycaemia.
On June 13, 2009, Diabetologia, the journal of European Association for the Study of Diabetes (EASD), published the results of a 5 year long-term observational, retrospective analysis. During the study no other safety issues, such as unexpected adverse events for either insulin emerged. However, insulin glargine was associated with a lower incidence of severe hypoglycaemia compared with NPH insulin.
Possible cancer link
On June 26, 2009, Diabetologia published the results of four large-scale registry studies from Sweden, Germany, Scotland and the rest of the UK. The German study, of around 127,000 insulin-treated patients from an insurance database, suggested a possible link between insulin glargine (Lantus) and increased risk of developing cancer. The risk of cancer was dose-dependent, with those taking higher doses of Lantus apparently at increased risk. Whilst the authors stressed the limitations of the study and recommended that patients prescribed Lantus continue to take the drug, the results led to the EASD making "an urgent call for more research into a possible link between use of insulin glargine (an insulin analogue, brand name Lantus) and increased risk of cancer."
The European Medicines Agency (EMEA) responded, stating that the results of the four studies were inconsistent, and that a relationship between insulin glargine and cancer could neither be confirmed nor excluded. They announced that they would undertake further detailed assessment of the studies’ results and any other relevant information, including several potential confounding factors that had not been fully taken into account by the studies. Patients being treated with insulin glargine were advised to continue their treatment as normal. The following month, the EMEA reported back, concluding that "the available data does not provide a cause for concern and that changes to the prescribing advice are therefore not necessary.”
The American Diabetes Association (ADA) also responded to the Diabetologia report, describing the published registry studies as “conflicting and confusing” and “inconclusive”. They advised patients against discontinuing Lantus and warned against "over-reaction".
References
- American Diabetes Association. (2003). Position statement: Insulin administration. Diabetes Care 26(Suppl. 1), 121–124
- EPAR Lantus, German summary of admission report of EMEA (PDF)
- , Action to Control Cardiovascular Risk in Diabetes (ACCORD), Trial , June 6, 2008
- , Effects of Intensive Glucose Lowering in Type 2 Diabetes
- L. Raymond Reynolds, MD, FACP, FACE, ECNU (2010). "Comparing Insulins Detemir and Glargine in Type 2 Diabetes: More Similarities than Differences". Postgraduate Medicine. 122 (1): 201–203. doi:10.3810/pgm.2010.01.2116. PMID 20107306.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H (2009). "Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis". CMAJ. 180 (4): 385–97. doi:10.1503/cmaj.081041. PMC 2638025. PMID 19221352.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - Rosenstock J, Fonseca V, McGill JB, Riddle M, Hallé JP, Hramiak I, Johnston P, Davis M. (13 June 2009). "Similar progression of diabetic retinopathy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study" (PDF). Diabetologia. 52 (9): 1778–88. doi:10.1007/s00125-009-1415-7. PMC 2723680. PMID 19526210.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Hemkens LG; et al. (26 June 2009). "Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study". Diabetologia. 52 (9): 1732–44. doi:10.1007/s00125-009-1418-4. PMC 2723679. PMID 19565214.
{{cite journal}}: Explicit use of et al. in:|author=(help) - http://webcast.easd.org/press/glargine/transcript.htm
- http://www.diabetologia-journal.org/cancer.html
- ^ European Medicines Agency update on safety of insulin glargine, June 29, 2009
- European Medicines Agency update on safety of insulin glargine, July 23, 2009
- Statement from the American Diabetes Association Related to Studies Published in 'Diabetologia', June 26, 2009
External links
- 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