The confirmatory results from two phase III trials have set the stage for a launch of degludec and DegludecPlus in 2013.
Novo Nordisk chief science officer Mads Krogsgaard Thomsen stated that, “We have said that we will submit in both Europe and the U.S. new drug applications for these products simultaneously if at all possible towards the end of next year, and that is still the case.”
The ultra-long effect of insulin degludec results from the slow release of insulin monomers from soluble multihexamers that form after subcutaneous injection, the authors of the current report explain. This produces a long half-life and a smooth and stable pharmacokinetic profile at steady state.
Dr. Kare I. Birkeland at Oslo University Hospital, Norway and colleagues conducted the 16-week open-label phase II trial, which involved 178 patients with Type 1 diabetes in five countries. They were randomized to receive insulin degludec, 600 or 900 micromol/L, or insulin glargine, injected subcutaneously daily before bedtime. All took insulin aspart at mealtimes.
At the end of the study, A1c was similar in the three arms at 7.8%, 8.0% and 7.6%, respectively. Fasting plasma glucose levels were 8.3, 8.3 and 8.9 mmol/L, respectively, according to the report.
The rate ratio for confirmed hypoglycemia was 0.72 for the lower-strength insulin degludec and 0.90 for the higher-strength formulation, compared to insulin glargine. Corresponding rate ratios for nocturnal hypoglycemia were 0.42 and 0.71.
As for side effects, “The frequency and pattern of adverse events was similar between insulin treatments,” the investigators found.
The results “strongly support” the continued clinical development of the 600-micromol/L formulation of insulin degludec, the authors say, but clinical development of the 900-micromol/L formulation has been discontinued.
It was evident that the rates of confirmed hypoglycemia (overall and nocturnal) were lower for IDeg compared with IGlar throughout the trial, indicating a better tolerability profile that was most apparent for IDeg(A). The trend for a lower rate of overall hypoglycemia for IDeg(A) versus IGlar (RR: 0.72 [0.52–1.00]) creates the opportunity for confirming this finding via similar treatment algorithms in larger, longer-term clinical trials. It remains to be proven whether it will be possible for patients treated with IDeg to achieve lower mean glycemic values at equivalent rates of hypoglycemia to other basal insulin preparations.
In summary, Dr. Birkeland and colleagues conclude, “This clinical trial showed that insulin degludec, used in combination with mealtime insulin aspart, is a well-tolerated and efficacious treatment when used in people with Type 1 diabetes, providing comparable glycemic control to insulin glargine at comparable doses, but with lower rates of hypoglycemia.”
Diabetes CareJanuary 26, 2011DC_101925