On Friday 26 June, 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 analogue, insulin glargine,
and cancer1. As a basis for such a possible link, an accompanying editorial
explains that certain insulin analogues have a structure making them more
likely to bind to the IGF-1 receptor which is known to be involved in promoting
tumour growth2.
Novo Nordisk markets three insulin analogues, Levemir® (insulin detemir), a
long-acting basal insulin analogue, NovoRapid®/NovoLog® (insulin aspart), a
short-acting insulin analogue, and NovoMix®/NovoLog® Mix 70/30 (biphasic
insulin aspart). To avoid unnecessary speculation about whether Novo Nordisk
insulin analogues 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 analogues 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 development3.
• Studies on receptor binding and cell growth together show that insulin
aspart, the insulin analogue present in NovoRapid®/NovoLog® and
NovoMix®/NovoLog®
Mix 70/30 has an in vitro safety profile that is identical to that of human
insulin3,4.
• Studies on receptor binding have shown that Levemir® 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® distinguishes itself from
insulin
glargine, which has been shown to have increased affinity for the IGF-1
receptor compared to human insulin4,5,6 .
• All Novo Nordisk insulin analogues on the market have been studied in many
randomised, 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 analogues.
• Novo Nordisk has over the last 20 years discovered and developed insulin
analogues to improve the treatment success rate for people with diabetes.
Extensive
clinical testing has provided evidence that Levemir®, NovoRapid®/NovoLog® and
NovoMix®/NovoLog® 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 analogues, together with the existence of
comprehensive insulin safety databases, convinces us that our insulin analogues
improve treatment outcomes in diabetes patients relative to human insulin.”
Conference call
On 29 June at 8 am CET, corresponding to 2 am 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 unfavourably changed due to alterations in the insulin
molecule that an insulin analogue can increase the risk of cell proliferation
via the IGF-1 receptor.
Novo Nordisk is a healthcare company and a world leader in diabetes care. In
addition, Novo Nordisk has a leading position within areas such as haemostasis
management, growth hormone therapy and hormone replacement therapy. Novo
Nordisk manufactures and markets pharmaceutical products and services that make
a significant difference to patients, the medical profession and society. 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 more information,
visit novonordisk.com.
Contacts for further information
Media: Investors:
Mike Rulis Mads Veggerby Lausten
Tel: (+45) 4442 3573 Tel: (+45) 4443 7919
mike@novonordisk.com mlau@novonordisk.com
Kasper Roseeuw Poulsen
Tel: (+45) 4442 4471
krop@novonordisk.com
In North America: In North America:
Sean Clements Hans Rommer
Tel: (+1 609-514-8316 Tel: (+1) 609 919 7937
secl@novonordisk.com hrmm@novonordisk.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, Schäffer L, Trüb 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, Schäffer L, Sørensen A, Kristensen C, Jonassen I, Schmid C, Trüb
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