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Levemir®: Patented structure and low affinity for the IGF-1 receptor1

Structure is associated with different IGF-1 receptor affinity1,2

The structure of Levemir is associated with different IGF-1 receptor affinity

Human insulin3

  • Structure comprises 51 amino acids, 21 of which constitute the A polypeptide chain and 30 of which comprise the B polypeptide chain, both linked by a disulfide bond
  • The baseline standard for determination of insulin-like growth factor-1 (IGF-1) receptor affinity of insulin analogs

Levemir®

  • Engineered by omitting an amino acid, threonine, in position B30 and attaching a fatty acid chain to the amino acid at B29
  • Low affinity for the IGF-1 receptor1

Additional information

Bruce W. Bode, MD, discusses insulin structure and affinity for the IGF-1 receptor and reviews clinical data on insulins.

Watch the eDetail Download the audio program

Low IGF-1 receptor affinity1

An in vitro study has been conducted on affinity for the IGF-1 receptor with insulin analogs1

In one study, Levemir® was shown to have low affinity for the IGF-1 receptor relative to human insulin1

Levemir was shown to have low IGF-1 receptor affinity

An in vitro study that compared the insulin- and IGF-1-receptor-binding properties and the metabolic and mitogenic potencies of the rapid-acting and long-acting insulin analogs with human insulin. IGF-1 receptor affinity was measured using purified human IGF-1 receptor.1

The clinical significance of the in vitro activity of the IGF-1 receptor has not been established.

Recent findings

No evidence of increased incidence of cancer diagnosis in patients with diabetes treated with Levemir®: a meta-analysis4

Treatment with Levemir® was associated with no increased incidence of cancer diagnosis, compared with NPH insulin4

Levemir showed no increased incidence of cancer diagnosis compared with NPH insulin

A meta-analysis of clinical studies of Levemir® sponsored by Novo Nordisk4

  • Reviewed results from 8693 patients in 21 randomized controlled trials
  • Compared the incidence of cancer diagnosis in patients treated with Levemir® with that of patients treated with human insulin (NPH insulin) or Lantus® (insulin glargine) during the trials
  • 16 of the included trials had NPH insulin as a comparator treatment
  • 5 of the 21 trials had insulin glargine as a comparator. These results are not reported here
  • Cancer incidence was not a predefined end point of the individual trials. Incidence was calculated from the databases of all adverse events from the included studies

A meta-analysis is a systematic method that uses statistical techniques for combining results from different studies to obtain a quantitative estimate of the overall effect of a particular intervention or variable on a defined outcome. These results were not a predefined end point of the individual trials. Additional long-term studies are required prior to reaching any conclusions on these data.

Meta-analyses may produce a stronger conclusion than can be provided by any individual study. Caution should be applied when reviewing results.

Related Support

Take a closer look at Levemir® and IGF-1 receptor affinity Watch Bruce W. Bode, MD, discuss insulin structure and affinity for the IGF-1 receptor and review clinical data on insulins. You can also download this audio program and take it with you.

View an interactive timeline of literature about IGF-1 receptor affinity Access selected publications about IGF-1 receptor affinity and cancer risk in diabetes treatment.

Up Next

Find information about Levemir® dosing and delivery

References:

  1. Kurtzhals P, Schäffer L, Sørensen A, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes. 2000;49(6):999-1005.
  2. Slieker LJ, Brooke GS, DiMarchi RD, et al. Modifications in the B10 and B26-30 regions of the B chain of human insulin alter affinity for the human IGF-1R receptor more than for the insulin receptor. Diabetologia. 1997;40(suppl 2):S54-S61.
  3. Data on file, Novo Nordisk, Inc., Princeton, NJ.
  4. Dejgaard A, Lynggaard H, Råstam J, Krogsgaard Thomsen M. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia. 2009;52(12):2507-2512.

  1. Levemir® (insulin detemir [rDNA origin] injection) Indications and Usage

    Levemir® is indicated for once- or twice-daily subcutaneous administration for the 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.

    Levemir® Important Safety Information

    Levemir® is contraindicated in patients hypersensitive to insulin detemir or one of its excipients.

    Levemir® should not be diluted or mixed with any other insulin preparations.

    Hypoglycemia is the most common adverse effect of all insulin therapies, including Levemir®. As with other insulins, the timing of hypoglycemic events may differ among various insulin preparations. Glucose monitoring is recommended for all patients with diabetes. Levemir® is not to be used in insulin infusion pumps. Any change of insulin dose should be made cautiously and only under medical supervision. Concomitant oral antidiabetes treatment may require adjustment.

    Needles and Levemir® FlexPen® must not be shared.

    Inadequate dosing or discontinuation of treatment may lead to hyperglycemia and, in patients with type 1 diabetes, diabetic ketoacidosis. Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Dose and timing of administration may need to be adjusted to reduce the risk of hypoglycemia in patients being switched to Levemir® from other intermediate or long-acting insulin preparations. The dose of Levemir® may need to be adjusted in patients with renal or hepatic impairment.

    Other adverse events commonly associated with insulin therapy may include injection site reactions (on average, 3% to 4% of patients in clinical trials) such as lipodystrophy, redness, pain, itching, hives, swelling, and inflammation. Less common but more serious are severe cases of generalized allergy, including anaphylactic reaction, which may be life threatening.

    *Whether these observed differences represent true differences in the effects of Levemir®, NPH insulin, and insulin glargine is not known since these trials were not blinded and the protocols (e.g., diet and exercise instructions and monitoring) were not specifically directed at exploring hypotheses related to weight effects of the treatments compared. The clinical significance of the observed differences in weight has not been established.

    Please click hereclick here for Prescribing Information.

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