Frequently Asked Questions

Insulin degludec is an ultra-long-acting basal insulin being developed by Novo Nordisk. Insulin degludec and insulin degludec / insulin aspart have been submitted to regulatory authorities for review but have not yet been approved for use.

 
What is insulin degludec?
Insulin degludec is a new ultra-long-acting once-daily basal insulin under development by Novo Nordisk1. It reduces blood glucose levels and several studies have shown that it significantly reduced the rates of hypoglycaemia (low blood sugar) in people with diabetes, particularly during night-time, compared to insulin glargine2,3.

Insulin degludec is also undergoing studies in which people with diabetes can take it at any time of the day and at different times from day to day when needed and still maintain stable glucose levels4,5. Clinical studies have shown that insulin degludec can be dosed 8 to 40 hours apart without losing equivalent overall glycaemic control, when compared to insulin glargine4,5.
How does insulin degludec work?
Once injected, insulin degludec forms long molecular chains, known as multi-hexamers. It is the only insulin to form multi-hexamers when injected, resulting in a soluble depot of insulin6 in the tissue.

The insulin degludec monomers (individual insulin molecules) break away from the ends of the multi-hexamers, similar to pearls coming off a string one at a time, and are slowly and continuously absorbed into circulation7.

This process ensures an ultra-long duration of action that can extend beyond 42 hours with a flat and stable profile6,8.
Why will patients benefit from this new treatment option?
Insulin is often under-utilised primarily due to the risk or fear of hypoglycaemia and inflexible dosing regimens. Available insulin treatments require patients to maintain a consistent dosing regimen, at the same time every day.

This need for consistency can impact patients’ everyday lives and can result in people with diabetes not being well controlled putting them at increased risk of developing the severe complications associated with diabetes9-15.
What is hypoglycaemia and what is significant about nocturnal hypoglycaemia?
Hypoglycaemia is a condition commonly associated with diabetes occurring when the concentration of glucose carried in the blood falls below the level the body needs to allow it to function ‘normally’16,17.

Symptoms of mild hypoglycaemia can include: pounding heart, trembling, hunger, sweating, and difficulty concentrating and/or confusion16,18.

Symptoms of severe hypoglycaemia can include seizure, coma and even death18 and is often linked to increased risk of diabetes-related complications, such as cardiovascular problems or neurological dysfunctions19,20.

Nocturnal hypoglycaemic events occur at night when people are sleeping and may be less conscious of the onset of symptoms. The most severe nocturnal events can be fatal, and may cause ‘dead in bed syndrome’, in which a victim dies suddenly after appearing to have been in good health during preceding days18,21,22.

In the large scale clinical trial programme, BEGIN™, insulin degludec was associated with a lower rate of hypoglycaemia, especially at night, compared to insulin glargine2,3.
What is insulin degludec/insulin aspart and how is it different from insulin degludec?
Insulin degludec/insulin aspart is a soluble insulin co-formulation of two insulins – comprised of ultra-long-acting insulin degludec and the most prescribed rapid acting insulin, NovoRapid®. It provides both fasting and post-prandial glucose control23,24.

Insulin degludec/insulin aspart has been studied in a large-scale clinical trial programme called BOOST™, which examined its ability to provide effective mealtime and full 24-hour basal control in a single injection23,24.
Please describe the clinical trial programmes, BEGIN™ and BOOST™?
Insulin degludec and insulin degludec/insulin aspart are being studied in the BEGIN™ and the BOOST™ programmes, respectively, which together comprise the largest clinical trial programme in the field of insulin therapy, with over 11,000 type 1 and type 2 diabetes patients. Novo Nordisk completed the phase 3a studies in 2010. The results comprise the majority of the data supporting the regulatory applications.
How will insulin degludec be administered?
Insulin degludec will be administered using FlexTouch®. FlexTouch® is the latest innovation in prefilled devices from Novo Nordisk25. It is a prefilled insulin pen with many user-friendly features designed to improve the experience of performing daily injections26-28.

FlexTouch® has demonstrated higher preference by patients and better dose accuracy than vial and syringe methods in clinical studies26-28. FlexTouch® is the first prefilled insulin pen with a unique spring-loaded dosing mechanism that prevents the push-button from extending, making it easier for patients to use25.
What is the regulatory status of insulin degludec and insulin degludec/insulin aspart?
Insulin degludec and insulin degludec/insulin aspart were submitted for regulatory approval for once-daily use to the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in September 2011.

In addition, Novo Nordisk has applied for approval of both compounds in Japan, Canada, Switzerland and a range of other countries.
 

References

1. Heise T, Hovelmann U, Nosek L, et al. Insulin degludec has a two-fold longer half-life and a more consistent pharmacokinetic profile than insulin glargine. Poster 1444, presented at International Diabetes Federation (IDF), Dubai, December 2011.
2. Heller S, Buse J, Fisher M et al. Insulin degludec, an ultra-long acting basal insulin, versus insulin glargine in basal bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN™ Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. The Lancet. 2012;379(9825):1489-97
3. Garber AJ, King AB, Del Prato S et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN™ Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. The Lancet. 2012;379(9825):1498-507
4. Birkeland KI, Raz I, Gough S, et al. Insulin degludec: similar glycaemic control and safety when given in a flexible daily dosing regimen or the same time daily in type 2 diabetes. Poster 1443, presented at International Diabetes Federation (IDF), Dubai, December 2011.
5. Bain S, Aitkin S, Gough S, et al. Flexible once-daily dosing of insulin degludec is as efficacious and safe as insulin glargine given the same time each day in type 2 diabetes. Oral 0508, presented at International Diabetes Federation (IDF), Dubai, December 2011.
6. Kurtzhals P, Heise T, Strauss HM, et al. Multihexamer formation is the underlying mechanism behind the ultra-long glucose-lowering effect of insulin degludec. Poster 1049, presented at European Association for the Studies of Diabetes (EASD), Lisbon, September, 2011.
7. Jonassen I, Havelund S, Hoeg-Jensen T, et al. Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin. Published online Pharm Res April 2012.
8. Nosek L, Heise T, Bøttcher SG, et al. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect. Poster 1452, presented at International Diabetes Federation (IDF), Dubai, December 2011.
9. Brunton S, Gough S, Hicks D, et al. Editorial - A look into the future: improving diabetes care by 2015. Curr Med Res Opin. 2011; 27(S3):65-72.
10. Peyrot M, Rubin RR, Lauritzen T, et al. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care. 2005; 28(11):2673-2679.
11. Peyrot M, Rubin RR, Kruger DF et al., Correlates of insulin injection omission. Diabetes Care. 2010: 33(2);240-245.
12. Randløv J and Ulrik Poulsen J. How much do forgotten insulin injections matter to haemoglobin A1c in people with diabetes? A simulation study. J Diab Sci Tech. 2008; 2(2):229-235.
13. Donnelly LA, Morris AD and Evans JM. Adherence to insulin and its association with glycaemic control in patients with type 2 diabetes. Q J Med. 2007; 100:345-350.
14. Peyrot M, Barnett AH, Meneghini LF et al. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabet Med. 2012;29:682–689.
15. Rubin RR. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med. 2005;118(5A):27S-34S.
16. American Diabetes Association. Common terms. Available at URL: http://www.diabetes.org/diabetes-basics/common-terms/common-terms-f-k.html Last accessed: April 2012.
17. Mayo Clinic. Hypoglycaemia. Available at URL: http://www.mayoclinic.com/health/hypoglycemia/DS00198. Last accessed: April 2012.
18. Cefalu CA and Cefalu WT. Controlling hypoglycemia in type 2 diabetes: Which agent for which patient? J Fam Pract. 2005;54(10):855-62.
19. Zoungas S, Patel A, Chalmers J, et al. Severe Hypoglycemia and Risks of Vascular Events and Deaths. N Engl J Med. 2010;363:1410–8.
20. Adler GK, Bonyhay I, Failing H, et al. Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function. Diabetes. 2009;58:360–6.
21. Allen KV and Frier BM. Nocturnal hypoglycemia: clinical manifestations and therapeutic strategies toward prevention. Endocr Pract. 2003;9(6):530-43.
22. Sovik O and Thordarson H. Dead-in-bed syndrome in young diabetic patients. Diabetes Care. 1999;22(S2):B40-2.
23. Niskanen L, Leiter LA, Franek E et al. IDegAsp, a soluble insulin combination of insulin degludec and insulin aspart, in type 2 diabetes: comparison to biphasic insulin aspart 30. Poster 1437, presented at International Diabetes Federation (IDF), Dubai, December 2011.
24. Hirsch I, Franek E, Courreges JP, et al. IDegAsp, a soluble insulin combination of insulin degludec and insulin aspart: basal-bolus treatment with insulin aspart in type 1 diabetes. Poster 1438, presented at International Diabetes Federation (IDF), Dubai, December 2011.
25. Hemmingsen H, Niemeyer M, Hansen MR, et al. A prefilled insulin pen with a novel injection mechanism and a lower injection force than other prefilled insulin pens. Diabetes Technol Ther. 2011;13(12):1207-11.
26. Wielandt JO, Niemeyer M, Hansen MR, et al. FlexTouch: A Prefilled Insulin Pen with a Novel Injection Mechanism with Consistent High Accuracy at Low- (1 U), Medium- (40 U), and High- (80 U) Dose Settings. J Diabetes Sci Technol. 2011; 5 (5):1195-1199.
27. Bailey T, Thurman J, Niemeyer M, et al. sability and preference evaluation of a prefilled insulin pen with a novel injection mechanism. Curr Med Res Opin. 2011; 27:2043–52.
28.Oyer D, Narendran P, Qvist M, et al. Ease of use and preference assessment of a new prefilled insulin pen versus a widely available prefilled insulin pen in people with diabetes, physicians and nurses. Expert Opin Drug Deliv. 2011;8(10):1259-69.

APROM ID# 4045. Date of Approval: May 2012