Insulin detemir

Insulin detemir
Mass / length primary structure	5.9  kDa
Identifier
External IDs	CAS number : 169148-63-4
Drug information
ATC code	A10 AE05
DrugBank	DB01307
Drug class	Antidiabetic drug

Insulin detemir (trade name Levemir ; manufacturer Novo Nordisk ) is a long-acting insulin analog for the treatment of diabetes mellitus . It was approved by the European Commission in June 2004 . The effect lasts for up to 24 hours, depending on the dose. It can be used in combination with blood sugar lowering drugs (oral antidiabetic agents ) or meal-related short or fast-acting insulin .

Clinical information

• Areas of application (indications): Insulin detemir is used in the treatment of diabetes mellitus in adults, adolescents and children aged 6 to 17 years.
• Type and duration of administration: Insulin detemir is a long-acting insulin analogue that is used as basal insulin . It is injected subcutaneously (under the skin) once or twice a day, depending on the therapy regimen . The dosage must be adjusted individually.
• Contraindications: In case of hypersensitivity or allergy to insulin detemir, the drug must not be used.
• Use during pregnancy and lactation : No clinical experience is available to date.

Pharmacological properties

• Mechanism of action (pharmacodynamics): Insulin detemir is a soluble, long-acting insulin analogue with a prolonged duration of action, which is used as basal insulin. The blood sugar lowering effect is based on the ability of the molecule to promote the uptake of glucose by binding to insulin receptors in muscle and fat cells . At the same time, the release of glucose from the liver is inhibited.
• Uptake and distribution in the body (pharmacokinetics): The maximum serum concentration is reached within 6 to 8 hours after administration. The delayed increase in concentration is achieved by myristic acid, which is attached to the B chain. This reversibly binds the insulin detemir to serum albumin, so that only about 1% circulates freely in the blood. The intra-individual variability of absorption is lower with insulin detemir than with other basal insulin preparations.

Other Information

• Chemical and pharmaceutical information: The C -terminal threonine (B30) was removed and a myristic acid molecule was condensed on the ε-amino function of the lysine on B29 . The pH of the preparation is 7.4. The prolonged effect of insulin detemir is mediated by the strong self-association of insulin detemir molecules at the injection site and the albumin binding via the fatty acid side chain.

Detemir
          ┌─────────┐
G-I-V-E-Q-C-C-T-S-I-C-S-L-Y-Q-L-E-N-Y-C-N
            │                       ┌─┘
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
                                                        │
                                                       HN-CO-C13H27

It is produced by genetic engineering from recombinant DNA in Saccharomyces cerevisiae . Additives are mannitol , phenol , m-cresol , zinc acetate , disodium hydrogen phosphate , sodium chloride , hydrochloric acid 2N (pH adjustment), sodium hydroxide 2N (pH adjustment), water for injections .

With regard to the IGF-1 receptor affinity, insulin analogues sometimes differ significantly. Insulin detemir has similar beneficial properties as human insulin . The binding to the IGF-1 receptor is comparable, if not lower, to that of human insulin.

Studies:
In studies that patients with has been shown to type 2 diabetes with insulin detemir compared to NPH insulin comparable HbA1c reach values, but with significantly lower risk of hypoglycemia . There are comparable results for type 1 diabetics .

Web links

• Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Levemir
• Entries in the NIH study registry
• Insulin detemir (Levemir)

Individual evidence

1. ↑ EPAR Levemir®; German summary of the approval report of the European Medicines Agency: (PDF)
2. ↑ Peter C. Heinrich, Matthias Müller, Lutz Graeve (Eds.): Löffler-Petrides Biochemistry and Pathobiochemistry . 9th, completely revised Edition. Springer Medicine, Berlin / Heidelberg 2014, ISBN 978-3-642-17971-6 , p. 457 .
3. ^ Scientific discussion for the approval of Levemir. (PDF, 556 kB) European Medicines Agency , November 15, 2004, p. 29 , accessed on April 12, 2010 (English). 
4. ↑ P. Kurtzhals, L. Schäffer, A. Sørensen, C. Kristensen, I. Jonassen, C. Schmid, T. Trüb: Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. In: Diabetes . 49, No. 6, 2000, pp. 999-1005, PMID 10866053 .
5. ↑ K. Hermansen, M. Davies, T. Derezinski, G. Martinez Ravn, P. Clauson, P. Home: A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add- on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. In: Diabetes Care . 29, No. 6, 2006, pp. 1269-1274, doi: 10.2337 / dc05-1365 , PMID 16732007 .
6. ↑ K. Hermansen, P. Fontaine, KK Kukolja, V. Peterkova, G. Leth, MA Gall: Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes. In: Diabetologia . 47 (4), 2004, pp. 622-629, doi: 10.1007 / s00125-004-1365-z , PMID 15298338 .

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