Basal/Bolus Therapy: New Basal Insulin
In the beginning insulin was discovered and developed by Banting and Best (and McLeod). During the next nine decades, various permutations of the hormone insulin were created; first with beef and pork sources and then with advent of molecular biology, human and analog insulin was discovered and marketed by various pharmaceutical companies.
First, a mini-review is in order. To replicate the actions of pancreatic beta islet cells, we must "think" like a pancreas. The pancreas produces basal insulin to metabolize glucose released by glycogen breakdown in the liver when in the fasting state and bolus insulin to cover carbohydrates and lower blood glucose levels. NPH, Lente, and UltraLente were considered basal or background insulin and were the only products readily available until 2001. These basal insulins were matched with bolus insulins such as "semi-lente" or "regular" insulin until the late 1990s when the first rapid acting analogs were developed (humalog, novolog, and then later Apidra). Finally, around 2001-2002, Glargine, a peakless insulin lasting approximately 24 hours was introduced as a serious competitor to NPH. The major benefit was the ability to closely mimic true basal insulin that does NOT peak and thus decreases the risk of hypoglycemia. By coupling peakless basal insulin along with a rapid acting analog insulin to cover meal and snack carbohydrates as well as lower high blood sugars, basal /bolus therapy via multiple daily injections became a very popular and safe form of insulin treatment. The insulin pump uses rapid acting insulin analog as basal (through constant infusion) and bolus amounts as required. The next player on the basal front was Detemir, another peakless insulin that lasts approximately 12-18 hours (by most reports). These two relatively peakless insulin are generally used either once daily (Glargine) or twice daily (Detemir). (Note that some people with insulin dependant diabetes use Glargine twice daily and Detemir once daily depending on the prescribing practices of their diabetologist.)
Enter Degludec (IDeg)!
Insulin degludec is new basal insulin that has an "ultra-long" action profile (see biochemical details in the following reference). In a recent paper published in Diabetes Care online ahead of print on January 26, 2011, by Birkeland et. al, "Insulin Degludec in type 1 Diabetes"), the authors compared the action of Degludec with that of Glargine as a basal insulin. The study was a randomized controlled trial to determine the efficacy and safety profile of Degludec when administered once every 24 hours with mealtime bolus insulin (aspart-novolog) in people with type 1 diabetes. Based on the molecular profile of Degludec, the authors hypothesized that there might be a decrease in hypoglycemic events as compared with Glargine along with similar glycemic control.
The study was a 16-week randomized trial wherein 178 subjects (mean age=45.8 years, range 18-75 years) were given either Glargine or Degludec (in two different doses) once daily in the evening along with aspart (novolog) at mealtimes. Thus, there were three arms of the study:
1. Glargine recepients (600 umol/ L- <23+/-11 units> baseline dose),
2. Degludec (smaller dose -600 umol/L-<31+/-15 units> baseline dose) and
3. Degludec (larger dose- 900 umol/L-<28+/-13 units> baseline dose).
(NOTE: In the Glargine and smaller dose Degludec group: 1 unit=6 nmol), in the larger dose Degludec group: 1 unit=9 nmol)
What were the results?
At 16 weeks, the average hb A1C was comparable between both groups as well as the fasting blood sugar. However, the mean rates of confirmed hypoglycemia were 28 percent lower for the Degludec group (lower dose) and 10 percent lower for the Degludec group (higher dose) as compared to Glargine. Even more significantly, the rates of nighttime hypoglycemia were 58 percent lower in the group that received the smaller dose of Degludec and 29 percent lower in the group that received the larger dose of Degludec as compared with Glargine. It is important to note that the average total daily doses of insulin were similar to baseline before the study. Lastly the frequency and type of adverse events were similar between the two basal insulins. The authors thus concluded that in this phase 2 trial, Degludec was a safe basal insulin with comparable glycemic control to Glargine (at similar doses), but with a decreased incidence of hypoglycemia.
However, as with all studies, there are limitations:
- Only a 16-week time frame. Will these trends continue over a longer time period?
- Small sample size (@180 people with type 1 diabetes).
- Children and adolescents under age 18 were excluded from the study (most of my patient population).
- Patients with severe recurrent hypoglycemia were excluded from the study. Will Degludec help decrease hypoglycemia in these people?
- This is a phase 2 study sponsored by the pharmaceutical company Novo Nordisk.
I will keep you posted about latest developments!