BERLIN – Insulin degludec, an investigational insulin with a prolonged half-life and a reportedly flatter pharmacokinetic profile with fewer high and low levels, showed a modest hypoglycemic edge over insulin glargine in a 52-week head-to-head comparison in patients with type 2 diabetes.
While insulin degludec (IDeg) ran statistically even with insulin glargine for total hypoglycemic episodes and for severe hyperglycemic episodes, the IDeg formulation led to significantly fewer nocturnal hypoglycemic episodes, with a relative risk reduction of 36%. However, because all hypoglycemic episodes were infrequent, the results showed an absolute reduction average of about 0.3 nocturnal episodes per patient on glargine to about 0.2 episodes per patient on degludec, Dr. Bernard Zinman reported at the meeting.
Mitchel L. Zoler/IMNG Medical Media
Dr. Bernard Zinman
"You need to treat four patients for a year to prevent one nocturnal episode. To me, that sounds like a good deal," said Dr. Zinman, director of the Centre for Diabetes at Mount Sinai Hospital in Toronto. In contrast, the study results also showed that 50 patients with type 2 diabetes would need IDeg treatment for a year to prevent one severe hypoglycemic episode, compared with glargine, he added.
"We want to encourage using insulin earlier in patients with type 2 diabetes, but many physicians are afraid of insulin because of [the associated risk of] hypoglycemia. I think that physicians will use degludec preferentially in patients at high risk for hypoglycemia," Dr. Zinman said in an interview. He included in this risk group younger patients with type 1 diabetes, patients with type 1 diabetes who take insulin as multiple-dose injections, patients maintained on a tight-control regimen, and patients with a history of hypoglycemia. The low numbers of hypoglycemia episodes seen in his results reflected selection of low-risk patients, he added. The results "underestimate the clinical value [of preventing hypoglycemia] because in routine clinical practice hypoglycemia is more of an issue" than it was in this trial.
An application to approve IDeg for treating patients with either type 1 or type 2 diabetes is pending before the Food and Drug Administration, and last July Novo Nordisk, the company developing the drug, said that it expected a FDA advisory committee to consider the application in November 2012.
The trial enrolled 1,030 patients with established type 2 diabetes inadequately controlled by metformin and possibly other oral drugs and no history of insulin treatment. The researchers randomized 773 patients to once-daily treatment with IDeg and 257 to a once daily regimen of insulin glargine, with the dosage titrated to achieve pre-breakfast plasma glucose of 3.9-4.9 mmol/L. The patients average 59 years old, their average body mass index was about 31 kg/m2, their average hemoglobin A1c was 8.2%, and they had type 2 diabetes for an average of about 9 years.
Throughout the 52-week study, average HbA1c levels in the two treatment arms tracked together and, at 1 year, the two groups had virtually identical average levels of about 7.3%. Fasting plasma glucose also tracked at similar rates in both arms during the study but, at 1 year, the average level was 0.43 mmol/L lower in the degludec group, a statistically significant difference. The average daily insulin dosage received by patients in each of the two arms was also virtually identical.
The rate of all confirmed hypoglycemia episodes was 18% lower among the IDeg-treated patients, compared with the controls, but this difference did not reach statistical significance. Severe hypoglycemia episodes – defined as events where the patient required help – showed an 86% relative risk reduction, but because the event rates in both arms was small this difference was also not statistically significant.
An additional analysis also looked at the incidence of hypoglycemic episodes during the maintenance phase of treatment in the study, after the first 16 weeks. During maintenance, the two arms failed to show a significant difference in any measure of hypoglycemic episodes except for nocturnal events, which degludec treatment cut by 49% relative to the glargine group, a statistically significant difference.
Other than hypoglycemia the two insulin analogues showed similar safety profiles.
The study was sponsored by Novo Nordisk, the company developing IDeg. Dr. Zinman said that he has been an advisor to Novo Nordisk, Merck, Sanofi-Aventis, and Boehringer Ingelheim, and research funding from Novo Nordisk, Merck, and Boehringer Ingelheim.