Pharmacology Update: Insulin Detemir Injection (Levemir®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has approved a new long-acting insulin analog produced by DNA technology. Insulin detemir is soluble insulin that is acylated with a 14-carbon fatty acid (myristic acid) to enhance binding to albumin. This binding provides a slow release from the injection sites as well as plasma albumin. Insulin detemir is marketed by Novo Nordisk as Levemir®.
Indications
Insulin detemir is indicated for once or twice-daily administration in the treatment of adult patients who require basal insulin.1
Dosage
Insulin detemir is administered subcutaneously once or twice-daily. The once-daily dose should be given with the evening meal or at bedtime. For twice daily dosing, one dose may be given with the evening meal, at bedtime, or 12 hours after the morning dose.1
Insulin detemir is available as a 10 mL vial, 3 mL PenFill® cartridge, 2 mL InnoLet®, and 3 mL FlexPen®.
Potential Advantages
Insulin detemir has been reported to provide more predictable glucose-lowering effect than NPH insulin or insulin glargine.2,3 It has also shown less weight gain than patients on NPH insulin in both type 1 and type 2 diabetics.3,4
Potential Disadvantages
Insulin determir should not be diluted or mixed with any other insulin preparations.1 Since insulin detemir is an insulin analog, the long-term effects are not known.
Comments
Insulin detemir is a human insulin analog resulting from the elimination of threonine at B30 and the acylation of myristic acid to lysine at B29. This results in a preparation that is soluble at neutral pH. The addition of the 14-carbon fatty acid allows binding to interstitial albumin as well as plasma albumin thus not only prolonging its action but also providing a smooth release of insulin.4 Under euglycemic clamp conditions, insulin detemir showed significantly lower within subject variation than NPH insulin or insulin glargine.2 This may be due to the fact that NPH insulin is injected as a suspension and insulin glargine precipitates at the injection site resulting in another source of variation (eg, dissolution). Glycemic control as assessed by HbA1c was as least as good as NPH insulin and insulin glargine in type 1 diabetics and NPH insulin in type 2 diabetics.1 Less weight gain and a lower risks of hypoglycemia and nocturnal hypoglycemia have been associated with insulin detemir than NPH insulin in both type 1 and type 2 diabetics.3,4 The pharmacokinetics of insulin detemir are consistent in children, adolescents, and adults.5 However insulin detemir is currently only indicated in adults. Insulin detemir has less affinity for the insulin receptor and insulin-like growth factor-1 receptor than human insulin and insulin glargine.4 The clinical relevance of this difference in affinity is not known. Insulin detemir is expected to cause less injection site discomfort as the solution of the former is neutral and the latter acidic.4 The cost of insulin detemir was not available at the time of this review.
Clinical Implications
Insulin detemir offers an alternative to NPH insulin and insulin glargine with a smoother release of insulin. However, improved glycemic control has not been clearly established although weight gain and hypoglycemic appears to be reduced. Long-term effect has not been established for this insulin analog.
References
1. Levemir Product Information. Novo Nordisk Inc. June 2005.
2. Heise T, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004;53:1614-1620.
3. Vague P, et al. 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;26:590-596.
4. Chapman TM, Perry CM. Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus. Drugs. 2004;64:2577-2595.
5. Danne T, et al. Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care. 2003;26:3087-3092.
The FDA has approved a new long-acting insulin analog produced by DNA technology.
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