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| ==Medical uses== | ==Medical uses== | ||
| '''Medical uses'''<br /> | |||
| ⚫ | |||
| ⚫ | There has been a study that suggests that the long acting insulins, which include insulin glargine, do not appear much better than neutral protamine Hagedorn (NPH) insulin.<ref>{{cite journal|last=Waugh|first=N|coauthors=Cummins, E, Royle, P, Clar, C, Marien, M, Richter, B, Philip, S|title=Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation|journal=Health technology assessment (Winchester, England)|date=2010 Jul|volume=14|issue=36|pages=1–248|pmid=20646668|doi=10.3310/hta14360}}</ref> Despite the fact that, among other problems, the study only appears to have only been performed on type 2 diabetics, it is often cited as a reason to deny this insulin to all diabetics. | ||
| In one short meta-analysis of insulin analogue use and several different kinds of diabetes published by Singh et al., the authors conclude that more research is needed to investigate insulin analogues, in all likelihood submitting a reference of their preliminary publication in an application for a research grant.<ref name=Singh2009>{{cite journal |author=Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H|title=Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis |journal=CMAJ|volume=180 |issue=4 |pages=385–97 |year=2009 |month=February |pmid=19221352 |pmc=2638025 |doi=10.1503/cmaj.081041|url=http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=19221352}}</ref> | |||
| Although there is a large population of diabetics who are denied access to Lantus based upon the above studies, this is simultaneously countered by a large population of type 1 diabetics who successfully use this insulin to manage their diabetes. | |||
| '''Discussion of Research'''<br /> | |||
| The results of the above studies themselves are not in agreement with the usual experiences of some individuals who use this insulin, nor with the initial data in animal and human studies presented in the drug approval process. It is of note that the first referenced study was performed only on type 2 diabetics. Additionally, as noted by the authors, and also by the initial FDA review, the criteria used to assess and define a hypoglycemic incident in some studies are subject to debate. They are admitted to be less than ideally chosen in the FDA application for review. | |||
| Both of these papers seem to strive to make an economic point regarding the financial value of glargine relative to other insulins. Market values of glargine relative to NPH, which is a much older insulin manufactured in the US and also Denmark, vary by country from much higher in the US, to just slightly higher in Spain. The conclusions reported by the authors of these studies, combined with the now refuted reported increase in the incidence of cancer, seem to have as an objective a reduction in the market value of glargine, with the aspired net result that it might be more financially available to poorer populations. | |||
| An additional possible explanation for the discrepancy in the results of these studies with former work may lie in the level of control of internal and external factors that may also influence blood sugar control in the subjects. Indeed, it would not be without precedent for such studies to be used to unknowingly evaluate the efficacy of other blood sugar regulating, or even carcinogenic, agents. Hence, the reported results should not be used to support or reject any given individual's use of glargine. | |||
| Type 1 and Type 2 diabetes are different diseases. There is a large community of both on-line and off-line diabetics who have used this insulin for many years, and are quite pleased with its performance. There is a database of over 127000 individuals who have used this insulin in Germany alone. | |||
| ===Mixing with other insulins=== | ===Mixing with other insulins=== | ||
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| 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.<ref>, German summary of admission report of ] (PDF)</ref> | 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.<ref>, German summary of admission report of ] (PDF)</ref> | ||
| Lantus, with over 10 years of history in the diabetic market, is available without a prescription in Canada and Spain, among other countries. It is often used by many diabetics in order to avoid large unanticipated precipitous drops in blood sugar at work or school or during sleep or exercise. | |||
| ==References== | ==References== | ||
Revision as of 20:34, 23 September 2013
Pharmaceutical compound| Clinical data | |
|---|---|
| Trade names | Lantus |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a600027 |
| Routes of administration | Subcutaneous |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.241.126  |
| Chemical and physical data | |
| Formula | C267H404N72O78S6 |
| Molar mass | 6063 g/mol g·mol |
| (what is this?) (verify) | |
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 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.
Medical uses
Medical uses
There has been a study that suggests that the long acting insulins, which include insulin glargine, do not appear much better than neutral protamine Hagedorn (NPH) insulin. Despite the fact that, among other problems, the study only appears to have only been performed on type 2 diabetics, it is often cited as a reason to deny this insulin to all diabetics.
In one short meta-analysis of insulin analogue use and several different kinds of diabetes published by Singh et al., the authors conclude that more research is needed to investigate insulin analogues, in all likelihood submitting a reference of their preliminary publication in an application for a research grant.
Although there is a large population of diabetics who are denied access to Lantus based upon the above studies, this is simultaneously countered by a large population of type 1 diabetics who successfully use this insulin to manage their diabetes.
Discussion of Research
The results of the above studies themselves are not in agreement with the usual experiences of some individuals who use this insulin, nor with the initial data in animal and human studies presented in the drug approval process. It is of note that the first referenced study was performed only on type 2 diabetics. Additionally, as noted by the authors, and also by the initial FDA review, the criteria used to assess and define a hypoglycemic incident in some studies are subject to debate. They are admitted to be less than ideally chosen in the FDA application for review.
Both of these papers seem to strive to make an economic point regarding the financial value of glargine relative to other insulins. Market values of glargine relative to NPH, which is a much older insulin manufactured in the US and also Denmark, vary by country from much higher in the US, to just slightly higher in Spain. The conclusions reported by the authors of these studies, combined with the now refuted reported increase in the incidence of cancer, seem to have as an objective a reduction in the market value of glargine, with the aspired net result that it might be more financially available to poorer populations.
An additional possible explanation for the discrepancy in the results of these studies with former work may lie in the level of control of internal and external factors that may also influence blood sugar control in the subjects. Indeed, it would not be without precedent for such studies to be used to unknowingly evaluate the efficacy of other blood sugar regulating, or even carcinogenic, agents. Hence, the reported results should not be used to support or reject any given individual's use of glargine.
Type 1 and Type 2 diabetes are different diseases. There is a large community of both on-line and off-line diabetics who have used this insulin for many years, and are quite pleased with its performance. There is a database of over 127000 individuals who have used this insulin in Germany alone.
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 in clinical trials.
Adverse effects
Cancer
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 and increased risk of developing cancer. The risk of cancer was dose-dependent, with those taking higher doses of insulin glargine 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 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 potentialconfounding 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 insulin glargine and warned against "over-reaction".
Type 2 diabetics who used insulin glargine had a 2.9-fold greater chance of cancer, while those who took the generic drug metformin had an 8 percent lower risk, according to a study presented on 9 December 2011 at the San Antonio Breast Cancer Symposium. Researchers examined medical records of 23,266 patients in southern Sweden.
The researchers were unable to identify which types of cancer were most common among insulin glargine users, said Hakan Olsson, lead researcher and professor of oncology at Lund University. They plan to follow the patients, and investigate different forms of treatment for Type 1 diabetes, including Novo Nordisk A/S’s long- acting insulin Levemir, to tease out any differences, he said.
“Women should be aware that diabetes and breast cancer may be related,” Olsson said in a telephone interview. “The diabetes itself could play a role in the development of cancer and now data is emerging that drug therapy may also be important in relation to cancer.”
Three studies completed in 2012 with large numbers of experimental subjects found no link between use of insulin glargine and cancer.
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. 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, allowing for the subcutaneous injection of a clear solution. The asparagine substitution prevents deamidization of the acid-sensitive glycine 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 (pharmacokinetic)
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.
Development
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.
Lantus, with over 10 years of history in the diabetic market, is available without a prescription in Canada and Spain, among other countries. It is often used by many diabetics in order to avoid large unanticipated precipitous drops in blood sugar at work or school or during sleep or exercise.
References
- Waugh, N (2010 Jul). "Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation". Health technology assessment (Winchester, England). 14 (36): 1–248. doi:10.3310/hta14360. PMID 20646668.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - 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) - American Diabetes Association (2003). "Position statement: Insulin administration". Diabetes Care. 26 (Suppl. 1): 121–124.
- Kaplan, W.; et al. (2004). "Effects of Mixing Glargine and Short-Acting Insulin Analogs on Glucose Control". Diabetes Care. 27 (11): 2739–2740. doi:10.2337/diacare.27.11.2739. PMID 15505016.
{{cite journal}}: Explicit use of et al. in:|last2=(help) - 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
- Article at www.businessweek.com, 'Sanofi’s Lantus Doubled Risk of Cancer in Study of Diabetics', by Michelle Fay Cortez, December 09, 2011.
- Reinberg, Steven (12th June, 2012). "No Cancer Risk From Long-Acting Insulin: Studies". philly.com. Retrieved 12th June, 2012.
{{cite news}}: Check date values in:|accessdate=and|date=(help) - Bolli, G.; et al. (1999). "Insulin analogues and their potential in the management of diabetes mellitus". Diabetologia. 42 (10): 1151–1167.
{{cite journal}}: Explicit use of et al. in:|author=(help) - EPAR Lantus, German summary of admission report of EMEA (PDF)
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