The investigational ultra–long-acting insulin degludec improves long-term glycemic control in patients with type 2 diabetes similar to insulin glargine but with a reduced rate of nocturnal and severe hypoglycemia, and greater weight loss, said Bernard Zinman, MD, Director of the Diabetes Center at Mount Sinai Hospital, Professor of Medicine, University of Toronto, and lead investigator of a randomized head-to-head comparison.
In this randomized, open-label, phase 3a, noninferiority, treat-to-target trial, 1030 adults with insulin-naive type 2 diabetes that was inadequately controlled with oral antidiabetic medications were randomized in a 3:1 ratio to insulin degludec or to insulin glargine. Both insulins were used once daily and were titrated to achieve self-measured blood glucose targets calibrated to plasma glucose values of 70 mg/dL to 89 mg/dL. The mean baseline hemoglobin (Hb) A1c level was 8.2%.
Completion rates were 79% with insulin degludec and 77% with insulin glargine by week 52 (ie, study end), at which time the mean HbA1c level declined by 1.06% with insulin degludec and by 1.19% with insulin glargine, meeting the study’s criterion for noninferiority. Reductions in fasting plasma glucose levels were significantly greater with insulin degludec (–67.7 mg/dL) compared with insulin glargine (–59.5 mg/dL).
The rates of nocturnal hypoglycemia were 36% lower with insulin degludec than with insulin glargine (0.25 vs 0.39 episodes per patient annually). “The difference in hypoglycemia rate corresponds to less than 8 patients needed to treat for a year with insulin degludec in place of insulin glargine to avoid 1 nocturnal hypoglycemic episode,” said Dr Zinman.
“Treating 100 patients for 1 year with insulin degludec would result in 13 fewer nocturnal hypoglycemic events compared to treatment with insulin glargine,” he added.
The overall rates of confirmed hypoglycemia were 1.52 versus 1.85 episodes per patient annually for insulin degludec and insulin glargine, respectively. Overall severe hypoglycemia was infrequent in both groups, but it was significantly lower with insulin degludec.
Adverse events occurring in >5% of patients were bronchitis, gastroenteritis, nasopharyngitis, upper respiratory tract infection, headache, diarrhea, vomiting, back pain, and cough. The mean weight gain was similar between the 2 groups.
In a separate meta-analysis comparing hypoglycemia between these 2 agents in more than 4300 patients, the rates of overall and nocturnal hypoglycemia were significantly lower with insulin degludec at similar levels of HbA1c, reported Robert E. Ratner, MD, Senior Research Scientist at MedStar Health Research Institute, Hyattsville, MD, and Professor of Medicine, Georgetown University, Washington, DC.
For this meta-analysis, hypoglycemia was defined as rates of self-reported confirmed hypoglycemia (plasma glucose <56 mg/dL or severe hypoglycemia requiring assistance) and nocturnal confirmed hypoglycemia (00:01 through 05:59 hours).
Compared with insulin glargine, insulin degludec resulted in a 17% lower rate of overall hypoglycemia and a 32% lower rate of nocturnal hypoglycemia in patients with type 2 diabetes, both of which were statistically significant. In patients with type 1 diabetes, there were 25% fewer episodes of nocturnal hypoglycemia in patients treated with insulin degludec.