Insulin detemir

Insulin Detemir (insulin with a fatty acid molecule attached Chapter 11)... 

Levemir (Insulin detemir) Recombinant long-acting human insulin analogue produced in S. cerevisiae Engineered devoid of B30 threonine and a C14 fatty acid is covalently attached to B29 lysine Novo Nordisk 2004 (EU)... 

Home, P. and Kurtzhals, P. 2006. Insulin detemir from concept to clinical experience. Expert Opinion on Pharmacotherapy 7(3), 325-343. 

Levemir (insulin detemir) Yes Vial, 3-mL pen cartridge and InnoLet... 

The basal insulin component may be provided by once- or twice-daily NPH or detemir, or once-daily insulin glargine. Most type 1 DM patients require two injections of all insulins except insulin glargine. All of the insulins (with the exception of insulin glargine) have some degree of peak effect that must be considered in planning meals and activity. Insulin glargine or insulin detemir is a feasible basal insulin supplement for most patients. 

Another approach to the development of long-lasting insulin is illustrated in an experimental product known as insulin detemir. This insulin analog is produced by adding a fatty acid to the end of the B-chain, increasing its ability to bond to albumin in the blood. After this bonding occurs, the insulin is released at a slow and constant rate over a period of at least 24 hours. 

Injection 100 unites/mL (insulin detemir [rDNA]) (Rx) Levem/r(Novo Nordisk)... 

Insulin detemir Treatment of adult and pediatric patients with type 1 diabetes mellitus or adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia. 

Insulin lispro, insulin aspart, insulin detemir, insulin glargine and insuline glulisine are human in-sullin analogues with the same mechanism of action. It should be noted however that the potency of insulin detemir was decreased four fold compared to human insulin. By changing amino acids on some locations absorption rates and the duration of action may be changed compared to human insulin. 

Detemir needs some special attention here. Insulin detemir differs from human insulin in that one amino acid has been omitted from the end of the B chain, and a fatty acid has been attached. Detemir s action is extended because its altered form makes that it is slowly released from the subcutaneous depot. More than 98% of detemir in the bloodstream is bound to albumin. Because it slowly dissociates from the albumin, it is available to the body over an extended period. 

Brand Name(s) Rong-Acting Insulin Glargine (Rantus Ultralente), Insulin Detemir (Revemir)... 

Insulin detemir, Levemir (Novo Nordisk) Human analog U100... 

Disposable insulin pens are also available for selected formulations. These are regular insulin, insulin lispro, insulin aspart, insulin glulisine, insulin glargine, insulin detemir, and several mixtures of NPH with regular, lispro, or aspart insulin (Table 41-4). They have been well accepted by patients because they eliminate the need to carry syringes and bottles of insulin to the workplace and while traveling. 

An alternative method of altering the duration of action of insulin is to use analogues in which there are amino acid substitutions. Analogues are listed in Table 3. Insulin aspart, insulin detemir, insulin glargine, and insulin lispro are all covered in separate monographs. 

Insulin aspart Insulin defalan Insulin detemir... 

Vague P, Selam JL, Skeie S, De Leeuw I, Elte JW, Haahr H, Kristensen A, Draeger E. Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart. Diabetes Care 2003 26(3) 590-6. 

Insulin detemir is a long-acting insulin analogue that lacks threonine at the B30 position and is acylated with a 14-carbon myristoyl fatty acid side-chain at the epsilon-amino group of the lysine in the B28 position. This stimulates binding to albumin and increases the half-life, extending its duration of action. 

In healthy volunteers, there was a dose-related increase in blood insulin concentrations after the administration of insulin detemir (2). However, there was no clear dose-response metabolic effect and individual variability was high. 

Insulin detemir has been compared with protamine zinc insulin in 59 patients with type 1 diabetes (3). All used insulin detemir for 6 weeks and protamine zinc insulin for 6 weeks in a randomized order. About 2.35 times higher doses of detemir were necessary than protamine zinc insulin. Fasting blood glucose concentrations were lower at the end of the detemir period and there were fewer attacks of hypoglycemia. 

In a 6-month, multinational, open, parallel-group comparison of insulin detemir and protamine zinc insulin in 448 patients with type 1 diabetes, the two treatments produced comparable HbAlc concentrations and fasting plasma glucose concentrations with less within-subject variation in fasting blood glucose with insulin detemir (4). The risk of hypoglycemia was 22% lower with insulin detemir and 34% lower for nocturnal hypoglycemia. 

Phase 3 trials have suggested that insulin detemir is... 

Danne T, Liipke K, Waite K, Von Schuetz W, Gall M-A. Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care 2003 26 3087-92. 

Hermansen K, Madsbad S, Perrild H, Kristensen A, Axelsen M. Comparison of the soluble basal insulin analogue insulin detemir with NPH insulin a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy. Diabetes Care 2001 24(2) 296-301. 

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