Degludec: A New Basal Insulin
Prior to 2001, there were only three basal insulins that were used in combination with either regular or rapid acting insulin. NPH and Lente were intermediate acting insulin (duration 10-12 hours) along with Ultralente (duration 24-36 hours). These basal insulins had peaks that could increase the risk of hypoglycemia. Presently, only NPH is available and is generally used with regular or rapid acting insulin in conventional split mixed insulin regimens of two or three shots per day. The main limitation of these basal insulins was the risk of hypoglycemia secondary to the pronounced peak often requiring snacks to "feed" the insulin.
In 2001, Glargine (Lantus), given once daily, was introduced as a 24-hour relatively peakless insulin to be used as a basal insulin in combination with rapid acting insulins. Basal/bolus therapy was thus truly introduced for those requiring intensive insulin therapy. Years later, Detemir, a 12-16 hour relatively peakless insulin (given once or twice daily), also was added to the basal insulin group. These two insulins have become known as the "basal" function in basal/bolus therapy.
A new product will soon enter the basal class. Degludec (IDeg) is basal insulin that forms soluble multihexamer assemblies after subcutaneous injection, resulting in an ultra-long action profile. Thus, Degludec has an action duration of more than 24 hours. As such, this new ultra-long acting insulin will not have to be injected on a daily basis.
Three research studies have been published in The Lancet.
The first studied insulin degludec, an ultra-long acting basal insulin once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16 week randomized, open label phase 2 trial (Zinman et. al, Volume 377, issue 9769, pages 924-931, 3/12/11).
The second studied insulin degludec, an ultra-longacting basal insulin versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes, a phase 3 randomized, open label, treat-to-target non-inferiority trial(Garber et. al, Volume 379, issue 9825, pages 1498-1507, 4/21/12, )in which the authors noted the effectiveness of the new basal insulin. Novo Nordisk funded both studies.
In the phase 2 trial, it was demonstrated that insulin degludec achieved comparable glycemic control compared to insulin glargine without additional adverse events and might reduce the frequency of injections due to its ultra-long action profile. Participants included ages 18-75 years with type 2 diabetes.
The more recent Lancet study (2) along with a companion study for patients with type 1 diabetes, insulin degludec, an ultra-long acting basal insulin vs. glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a phase 3, randomized, open label, treat-to-target non-inferiority trial (Heller et. al Volume 379, Issue 9825, pages 1489-1497, 4/21/12) was aimed to compare the efficacy and safety of insulin degludec as compared with insulin glargine in the treatment of patients with type 1 and 2 diabetes. The study concluded that rates of nocturnal hypoglycemia in patients with both type 1 and type 2 diabetes decreased by 25 percent compared to insulin glargine. In both studies, the authors adjusted insulin sequentially to try to achieve a targeted fasting blood sugar level. Participants in both studies achieved similar improved glycemic control. Once again, Novo Nordisk funded both studies.
What are some limitations of these studies?
1. The pharmaceutical company funded studies.
2. An ultra-long acting basal insulin that is given three times a week may lead to the possibility of forgetting to give the insulin. It may be actually be more difficult to remember to give the insulin every other day instead of once daily.
3. Degludec has not been tested in people younger than 18 years of age as of yet.
4. More studies will need to be conducted prior to approval by the FDA and general use.
NEXT: super-rapid analog insulin