Results from trials in patients with T1DM and T2DM are consistent and suggest comparable glycemic lowering between insulin degludec and the basal insulin analogs detemir and glargine, with less frequent nocturnal hypoglycemia in those treated with insulin degludec compared with insulins glargine and detemir (FIGURE 2).
Flexibility of Dosing Time
Optimal glycemic benefits are achieved with the injection of basal insulin at a consistent time each day. However, consistent timing may be difficult owing to patients’ busy or erratic schedules and/or in patients who may at times forget to administer their medications. These patient factors can lead to wide variability in the dosing interval and suboptimal results in fasting glucose control. These challenges may be improved upon with the investigational agent insulin degludec due to the stable and prolonged time-action profile of insulin degludec coupled with low within-subject pharmacodynamic variability, allowing for a more flexible once-daily dosing time. A 26-week, randomized, open-label trial in patients with T2DM (N = 459) aimed to compare insulin degludec in the setting of variable dosing intervals by administering insulin degludec once daily using a flexible regimen compared with insulin glargine given once daily at the same time each day.18 Both insulins were added to an existing regimen of oral glucose-lowering therapy (if any) and titrated to achieve FPG <90 mg/dL. To ensure variability in the dosing interval, the once-daily regimen of insulin degludec involved a compulsory, rotating morning and evening schedule, creating 8- to 40-hour dosing intervals. From a baseline mean of 8.4%, A1C values were reduced by 1.28% and 1.26% with insulin degludec and insulin glargine, respectively, at 26 weeks, confirming noninferiority of the flexible regimen of once-daily insulin degludec compared with insulin glargine given at the same time each day. The mean FPG at week 26 was significantly lower for insulin degludec than insulin glargine (104 vs 112 mg/dL, respectively; P = .04). The rates of confirmed hypoglycemia (3.6 vs 3.5 episodes/patient-year) and nocturnal hypoglycemia (0.6 vs 0.8 episodes/patient-year) for insulin degludec compared with insulin glargine, respectively, and the numbers of severe hypoglycemia events (2 episodes/group), were similar between treatment groups. This trial demonstrates that when needed to accommodate changes in the patient’s daily schedule, insulin degludec may be administered at differing times from day to day without compromising glycemic control or safety compared with insulin glargine administered at the same time each day.
CONCLUSIONS
Insulin degludec, an ultra–long-acting basal insulin analog, possesses several desirable attributes. Findings from clinical trials have demonstrated that the new-generation once-daily basal insulin degludec provides similar A1C control compared to insulin glargine both administered as basal-oral therapy or in combination with insulin aspart, with the added benefit of lower rates of hypoglycemia, particularly nocturnal hypoglycemia. Insulin degludec has also been shown to offer dosing flexibility, with administration at any time of the day without compromising glycemic control or safety. Insulin degludec, pending FDA approval, will be an additional treatment to help patients with T1DM or T2DM achieve glycemic control.