Glucose-Lowering Effect of Insulin Degludec

San Diego—In a randomized, double-blind, 2-period, crossover trial, researchers found the glucose-lowering effect of insulin degludec was evenly distributed in the first and second 12-hour periods in patients with type 2 diabetes. They also concluded that the drug had a duration of action beyond 26 hours, according to a late-breaking poster titled Ultra-Long-Acting Insulin Degludec Has a Flat and Stable Glucose-Lowering Effect presented at the ADA meeting. Insulin degludec, an ultra-long-acting basal insulin, is injected subcutaneously once daily in patients with type 2 diabetes and is slowly absorbed. According to the authors, the drug’s ultra-long glucose-lowering effect has exceeded 40 hours in previous trials. This study examined insulin degludec’s glucose-lowering effect during a 24-hour dosing interval at steady state in 49 insulin-treated subjects with type 2 diabetes who did not take concomitant oral antidiabetic agents. They were randomly assigned to receive 0.4, 0.6, or 0.8 U/kg of insulin degludec administered once daily for 6 days. Between treatments, there was a washout period of 13 to 21 days. At the end of the treatment period, subjects underwent a 26-hour euglycemic clamp. Of the 49 patients, 40 were male and all were white. The mean age of the participants was 59 years, mean body mass index was 29.6 kg/m2, mean duration of type 2 diabetes was 14 years, and mean hemoglobin A1c level at baseline was 7.6%. During the 24-hour dosing interval, the total glucose-lowering effect increased with the increasing dose. The authors assessed the glucose-lowering effect by estimating the ratio between the area under the curve for the glucose infusion rate profiles compared with the total area under the curve during the 24 hours. In each of the 3 doses, the glucose-lowering effect was flat and stable. Within the 26-hour clamp, the blood glucose level did not reach the end of action of 150 mg/dL for any of the patients. In addition, the mean blood glucose levels remained at the target level until the end of the 26 hours. The clamp blood glucose level began at 90 mg/dL, and during the last 10 minutes of the dosing interval the mean blood glucose level was between 90 and 92 mg/dL at each of the doses. Thus, the authors concluded that insulin degludec’s duration of action lasted for >26 hours for all 3 doses. When assessing insulin degludec’s safety profile, the authors did not identify any safety concerns and found the drug was well tolerated. This study was supported by Novo Nordisk.