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Levemir® has a low affinity for IGF-1R1

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



Human insulin

  • 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 receptor (IGF-1R) 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 B29
  • Low affinity for IGF-1R1

Insulin glargine3

  • Engineered by adding 2 amino acid arginine residues to C-terminal B31 and B32 positions, and substituting glycine for asparagine at position A21
  • Affinity for IGF-1R that is approximately 6-fold that of human insulin1,4

In vitro studies have been conducted on affinity for IGF-1R of insulin analogs1,4

In one study, Levemir® was shown to have low affinity for IGF-1R relative to human insulin.1

An in vitro study that compared the insulin- and IGF-1R-binding properties and the metabolic and mitogenic potencies of the rapid-acting and long-acting insulin analogs with human insulin. IGF-1R affinity was measured using purified human IGF-1R.‡
Adapted from Kurtzhals et al, 2000.1

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

†Human insulin is the benchmark against which IFG-1R affinity was measured.

In another study, the IGF-1R affinity of insulin glargine was evaluated relative to human insulin.4

An in vitro study that evaluated the insulin- and IGF-1R-binding affinities and metabolic and mitogenic potencies of insulin analogs compared with human insulin. IGF-1R affinity was measured using membrane-bound human IGF-1R.‡
Adapted from Kohn et al, 2007.4

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

Levemir® was not evaluated in this study.
†Human insulin is the benchmark against which IGF-1R affinity was measured.

No evidence for increased incidence of cancer diagnosis in patients with diabetes treated with Levemir®: a meta-analysis5

Treatment with Levemir® was associated with no increased incidence of cancer diagnosis compared with NPH insulin.



A meta-analysis of clinical studies of Levemir® sponsored by Novo Nordisk5

  • Reviewed results from 8653 patients in 21 randomized controlled trials
  • Compared the incidence of cancer diagnosis in patients treated with Levemir® (insulin detemir) 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 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 endpoint 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.

Formulary lookup

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. Lantus® [package insert]. Bridgewater, NJ: sanofi-aventis US LLC; 2007.
  4. Kohn WD, Micanovic R, Myers SL, et al. pl-shifted insulin analogs with extended in vivo time action and favorable receptor selectivity. Peptides. 2007;28(4):935-948.
  5. 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 see Prescribing InformationPrescribing Information.

FlexPen® and Levemir® are registered trademarks of Novo Nordisk A/S. NovoMedLink™ is a trademark of Novo Nordisk A/S.