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Medical uses[edit]

The long acting insulins, which includes insulin glargine, do not appear much better than neutral

 protamine Hagedorn (NPH) insulin  but have a significantly greater cost making them, as of 2010, not cost effective.

[1] It is unclear if there is a difference in hypoglycemia and not enough

data to determine any differences with respect to long term outcomes.[2] 

Mixing with other insulins[edit] 

Unlike some other longer-acting insulins, glargine must not be diluted or mixed with other insulin or solution in the same syringe.

[3] However, this restriction has been questioned in clinical

trials.[4]

 

Adverse effects[edit]

Cancer[edit] 

On June 26, 2009, Diabetologia published the results of four large-scale registry studies fromSweden, 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 .[5]

 The risk of cancer was dose-dependent, withthose taking higher doses of insulin glargine apparently at increased risk .

[6] 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 ."[7]

 

The European Medicines Agency (EMEA) responded, stating that the results of the four studieswere inconsistent, and that a relationship between insulin glargine and cancer could neither beconfirmed nor excluded.

[8] 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. 

[8] 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.”[9]

 

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 glargineand warned against "over-reaction".[10]

 

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 presentedon 9 December 2011 at the San Antonio Breast Cancer Symposium. Researchers examined

medical records of 23,266 patients in southern Sweden.

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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 atelephone 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.” [11]

 

Three studies completed in 2012 with large numbers of experimental subjects found no link 

 between use of insulin glargine and cancer. [12]

 

Pharmacological specifications[edit]

Mechanism of action (pharmacodynamics)[edit] 

Insulin glargine have substitution of glycine for asparagine at A21 and two arginines added tothe 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.[13]

 It

can achieve a peakless level for at least 24 hours.

Acceptance and repartition in the body (pharmacokinetic)[edit] 

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 insulinhexamers. 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[edit]

The development of insulin glargine was conducted at Sanofi-Aventis's biotechnologycompetence 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 Lantusaround 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.

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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 Lantuscreated 3000 jobs in Berlin and Frankfurt-Höchst.

On June 9, 2000 the European Commission formally approved the launching of Lantus bySanofi-Aventis Germany Ltd. in the entire European Union. The admission was prolonged on

June 9, 2005.[14]