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Last updated on April 19, 2014 at 13:20 EDT

Novo Nordisk Insulin Analogs Have Proven Safety Profiles

June 28, 2009

PRINCETON, N.J., June 28 /PRNewswire/ — On Friday June 26, Diabetologia, the journal of the European Association for the Study of Diabetes (EASD) published online data from four studies relating to a possible link between a long-acting insulin analog, insulin glargine, and cancer(1). As a basis for such a possible link, an accompanying editorial explains that certain insulin analogs have a structure making them more likely to bind to the IGF-1 receptor which is known to be involved in promoting tumor growth(2).

Novo Nordisk markets three insulin analogs, Levemir(R) (insulin detemir), a long-acting basal insulin analog, NovoRapid(R)/NovoLog(R) (insulin aspart), a short-acting insulin analog, and NovoMix(R)/NovoLog(R) Mix 70/30 (biphasic insulin aspart). To avoid unnecessary speculation about whether Novo Nordisk insulin analogs may be associated with an increased risk of cancer, the company wishes to highlight the following:

  • For the past 20 years, all Novo Nordisk insulin analogs have been tested for IGF-1 receptor binding in the early research phase and only insulins with a binding ratio between the insulin and IGF-1 receptors similar to, or better than, that of human insulin have been accepted for further development(3).
  • Studies on receptor binding and cell growth together show that insulin aspart, the insulin analog present in NovoRapid(R)/NovoLog(R) and NovoMix(R)/NovoLog(R) Mix 70/30 has an in vitro safety profile that is identical to that of human insulin(3,4).
  • Studies on receptor binding have shown that Levemir(R) in comparison to human insulin has a relative affinity to the IGF-1 receptor which is equal to or slightly lower than to the insulin receptor(4,5). Levemir(R) distinguishes itself from insulin glargine, which has been shown to have increased affinity for the IGF-1 receptor compared to human insulin(4,5,6).
  • All Novo Nordisk insulin analogs on the market have been studied in many randomized, controlled trials, in observational studies and are furthermore monitored for any safety signals through rigorous post-marketing safety surveillance. Novo Nordisk has not identified any cancer signals for any of the three insulin analogs.
  • Novo Nordisk has over the last 20 years discovered and developed insulin analogs to improve the treatment success rate for people with diabetes. Extensive clinical testing has provided evidence that Levemir(R), NovoRapid(R)/NovoLog(R) and NovoMix(R)/NovoLog(R) Mix 70/30 possess clinical advantages for many patients with diabetes compared to human insulin.

Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, says: “Our science-driven approach to the discovery and development of safe, improved insulin analogs, together with the existence of comprehensive insulin safety databases, convinces us that our insulin analogs improve treatment outcomes in diabetes patients relative to human insulin.”

Conference call

On June 29 at 8 a.m. CET, corresponding to 2 a.m. EDT, a conference call for investors will be held. Investors will be able to listen in via a link on the investor section of novonordisk.com. Presentation material for the conference call will be made available approximately one hour before on the same page.

About insulin and IGF-1 receptors

Insulin can bind to two different receptors: insulin and IGF-1 (insulin-like growth factor-1) receptors. The former mainly causes glucose lowering whereas the latter mainly induces cell proliferation. Insulin binds much stronger (more than 500-fold) to the insulin receptor than to the IGF-1 receptor and it is if this binding profile is unfavorably changed due to alterations in the insulin molecule that an insulin analog can increase the risk of cell proliferation via the IGF-1 receptor.

Prescribing Information for Levemir(R), NovoLog(R) and NovoLog(R) Mix 70/30 is available by contacting Novo Nordisk or visiting novonordiskcare.com.

About Levemir(R), NovoLog(R) and NovoLog(R) Mix 70/30

Indications and Usage:

Levemir(R) (insulin detemir [rDNA origin] injection) is indicated for once- or twice-daily subcutaneous administration for the treatment of adult and pediatric patient with type 1 diabetes mellitus or adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia. NovoLog(R) (insulin aspart [rDNA origin] injection) is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus. NovoLog(R) Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection, [rDNA origin]) is indicated for the treatment of patients with diabetes mellitus for the control of hyperglycemia.

Important Safety Information:

Hypoglycemia is the most common adverse effect of insulin therapy, including Levemir(R), NovoLog(R), and NovoLog(R) Mix 70/30. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin dose should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, species, or method of manufacture may result in the need for a change in dosage.

Levemir(R), NovoLog(R) and NovoLog(R) Mix 70/30 are contraindicated during episodes of hypoglycemia and in patients hypersensitive to any of their excipients.

Potential side effects associated with the use of all insulins include hypoglycemia, hypokalemia, lipodystrophy, and allergic reactions. Less common but more serious area severe cases of generalized allergy, including anaphylactic reaction, which may be life threatening. Other adverse events commonly associated with insulin therapy may include injection site reactions such as lipodystrophy, redness, pain, itching, hives, swelling and inflammation. Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. The dose of any insulin may need to be adjusted in patients with renal or hepatic impairment.

Levemir(R) should not be diluted or mixed with any other insulin preparations. Concomitant oral antidiabetes treatment may require adjustment. Levemir(R) is not to be used in insulin infusion pumps. Inadequate dosing or discontinuation of treatment may lead to hyperglycemia and, in patients with type 1 diabetes, diabetic ketoacidosis. 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.

NovoLog(R) has a more rapid onset and shorter duration of action than regular human insulin. An injection of NovoLog(R) should be immediately followed by a meal within 5 to 10 minutes. Because of the short duration of action of NovoLog(R), a longer-acting insulin should also be used in patients with type 1 diabetes and may be needed in patients with type 2 diabetes. When used in an external subcutaneous insulin infusion pump, NovoLog(R) should not be mixed with any other insulin or diluent. Glucose monitoring is recommended for all patients with diabetes and is particularly important for patients using external pump infusion therapy. As with all insulin preparations, the time course of action of NovoLog(R) may vary in different individuals or at different times in the same individual and is dependent on many conditions, including injection site, local blood supply, temperature, and level of physical activity. Insulin, particularly when given intravenously or in settings of poor glycemic control, may cause hypokalemia.

Because NovoLog(R) Mix 70/30 has peak pharmacodynamic activity 1 hour after injection, it should be administered with meals. Because of differences in the action of NovoLog(R) Mix 70/30 and other insulins, care should be taken in patients in whom these conditions may be clinically relevant (e.g., patients who are fasting, have autonomic neuropathy, are using potassium-lowering drugs, or are taking drugs sensitive to serum potassium level). Do not mix NovoLog(R) Mix 70/30 with any other insulin product. Changes in cross-reactive antibodies were more common after NovoLog(R) Mix 70/30 than with human premixed 70/30, but the clinical significance of these antibodies has not been established.

About Novo Nordisk

Novo Nordisk is a healthcare company with an 86-year history of innovation and achievement in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition to diabetes care, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk’s business is driven by the Triple Bottom Line: a commitment to social responsibility to employees and customers, environmental soundness and economic success. With headquarters in Denmark, Novo Nordisk employs more than 27,900 employees in 81 countries, and markets its products in 179 countries. Novo Nordisk’s B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol ‘NVO’. For global information, visit novonordisk.com; for United States information, visit novonordisk-us.com.

References:

(1) www.diabetologia-journal.org/

(2) Baserga R, Peruzzi F, Reiss K (2003): The IGF-1 receptor in cancer biology. Int J Cancer 107: 873-877

(3) Gammeltoft S, Hansen BF, Dideriksen L, Lindholm A, Schaffer L, Trub T, Dayan A, Kurtzhals P (1999): Insulin aspart, a novel rapid-acting human insulin analogue. Exp Opin Invest Drugs 8 (9): 1431-1442

(4) Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T (2000): Correlations of receptor binding and metabolic and mitogenic potenticies of insulin analogs designed for clinical use. Diabetes 49: 999-1005

(5) Center for Drug Evaluation and Research, FDA. Application number 21-536: Pharmacology review of insulin detemir

(6) Shukla A, Grisouard J, Ehemann V, Hermani A, Ensmann H, Mayer D (2009) Analysis of signalling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines. Endocrine-Related Cancer 16: 429-441

SOURCE Novo Nordisk


Source: newswire