Insulin glargine
Encyclopedia
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.
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.
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.
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".
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
under the name Lantus, is a long-acting basal insulin analogue, given once daily to help control the blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
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
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
(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
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
(in some cases) or latent autoimmune diabetes of adults
Latent autoimmune diabetes
Latent Autoimmune Diabetes of Adults , also known as, Diabetes Type 1.5, is a term coined by Tuomi et al. in 1993 to describe slow-onset Type 1 autoimmune diabetes in 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.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), 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.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. However, this restriction has been successfully challenged in trials conducted by Kaplan, Rodriguez, Smith, Haymond, and Heptulla of Texas Childrens Hospital. .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. people with diabetes 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
European Association for the Study of Diabetes
The European Association for the Study of Diabetes is an scientific association founded in Montecatini, Italy in 1965 with Dr. Joseph Hoet as Founding President...
(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)
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
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
Confounding
In statistics, a confounding variable is an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable...
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
American Diabetes Association
The American Diabetes Association is a United States-based association working to fight the consequences of diabetes, and to help those affected by diabetes...
(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".
External links
- Insulin glargine - MedlinePlusMedlinePlusMedlinePlus is a free Web site that provides consumer health information for patients, families, and Health care providers. The site brings together information from the United States National Library of Medicine, the National Institutes of Health , other U.S. government agencies, and...
- 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