Novo Nordisk Insulin Analogs Have Proven Safety Profiles
2009年6月29日 - 4:18AM
PRニュース・ワイアー (英語)
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)
http://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
http://www.newscom.com/cgi-bin/prnh/20020404/NVOLOGODATASOURCE:
Novo Nordisk CONTACT: Mike Rulis, +45-4442-3573, ; In North
America, Sean Clements, +1-609-514-8316, ; or Investors, Mads
Veggerby Lausten, +45-4443-7919, , or Kasper Roseeuw Poulsen,
+45-4442-4471, , In North America, Hans Rommer, +1-609-919-7937,
Web Site: http://www.novonordisk.com/
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