Irl Hirsch, Bruce Bode, Jean-Pierre Courreges, et. al, published the latest information on the newest basal insulin-Degludec in Diabetes Care (published ahead of print online: DOI: 10.2337/dc11-2503 on August 28, 2012): Insulin Degludec/Insulin Aspart Administered once daily with any meal, with insulin aspart at other meals versus a standard Basal/bolus regimen in patients with type 1 diabetes.
The trial was a 26-week, phase 3, randomized open-label, treat–to-target trial.
Let us review the types of insulins briefly. Basal insulin is background insulin that is given to cover blood sugars when not eating. This is the type of insulin the pancreas normally produces between meals and overnight. Examples include: NPH insulin (peaks and lasts approximately between 8-10 hours), Glargine (peakless insulin and lasts approximately 24 hours), Detemir (peakless insulin and lasts approximately between 12-16 hours). Degludec is a newly developed long acting insulin that lasts approximately 40 hours and beyond. Degludec/aspart is a combination of both Degludec and Aspart currently in clinical development and therefore undergoing application in clinical trials. Bolus insulins include regular (lasting about 2-4 hours) and the rapid acting analog insulins: aspart, lispro, and actrapid. Basal/bolus therapy employs the combination of both basal insulin as background and bolus insulin to cover carbohydrates and to lower blood sugar.
What did the authors do?
548 adults with type 1 diabetes with hb A1cs ranging from 7 to 10 percent were randomized 2:1 in a 26-week, multinational, parallel group, treat–to-target trial to Degludec/Aspart (IDeg/Asp) or Detemir (IDet). IDeg/Asp was given with a meal and IDet was given in the evening, with a second breakfast dose added if required. (Author’s note: two doses of Detemir are typically required on our patient population.)
What were the results?
- Non-inferiority for IDeg/Asp verus IDet was confirmed. What does this mean? IDeg/Asp works just as well as IDet! That means that several injections have the potential to be eliminated in a typical basal/bolus therapy.
- Hb A1c improved by 0.75 percent with IDeg/Asp and 0.70 percent with IDet to 7.6 percent in both groups.
- There was no statistically significant difference between IDeg/Asp and IDet in rates of severe hypoglycemia (56 mg/dl).
- Nocturnal hypoglycemia rate was 37 percent lower with IDegA/Asp and IDet respectively (P<0.05).
- Total insulin dose was 1.3 percent lower in the IDeg/Asp group (P<0.0001).
- No treatment differences noted in health-related quality of life, laboratory measurements, physical examination, vital signs, EKGs, fundoscopy, or adverse events.
The key take-home message is that “efficacy of IDegAsp was established with fewer daily injections (3 vs. 4-5) and a lower insulin dose, and IDegAsp was also associated with a significantly lower risk of nocturnal hypoglycemia.”
So, where are we now?
This study demonstrates supportive information for the new combination of Insulins Degludec and Aspart. But, we are not quite ready for prime time! However, any means by which we can reduce the number of insulin injections is clearly an improvement for patient care and quality of life. There are, indeed, limitations to this study and for general adoption of this form of therapy.
The study was funded by Novo-Nordisk, the pharmaceutical company. This is often necessary for support of research, but it must always be kept in mind in terms of possible bias. Second, the research was conducted on adult subjects. Third, one must always be concerned with “simplicity.” The fact that a combination insulin of both basal and bolus will be employed with bolus insulin separately may be confusing in addition to the fact that Degludec will not be given on a routine day-to-day basis. It will be imperative to remember when one is due for their degludec or degludec/asp injection. (This sort of thing is reminiscent of the need to change insulin pump infusion sets every 2-3 days.) Keep in mind that the more complicated a regimen, the more likely there is to make errors… and less likely to adopt! However, this study clearly demonstrates progress in the effort to develop longer-acting basal insulins that have the ability to decrease both hypoglycemia overall as well as the more frightening hypoglycemia that can occur overnight.
I will keep you posted with further advancements in the development of new insulin products and combinations.