Previous studies compared insulin degludec with insulin glargine or detemir and showed that glycemic control was similar, but the frequency of nocturnal hypoglycemia was lower in the degludec group [18–23
]. Heise et al. [24
] showed degludec had a significantly more predictable glucose-lowering effect from day to day variability than glargine. However, no previous study assessed the changes of blood glucose or compared insulin doses just after switching to insulin degludec. The present study demonstrated the changes of glucose fluctuation and insulin dosage immediately after switching from insulin glargine or detemir to insulin degludec in patients with Japanese T1DM.
In this study, CGM did not reveal any significant changes of the AUC 0000–0600 hours, or the frequency of hypoglycemia after switching to insulin degludec. In the once-daily group, switching to insulin degludec was performed with the same dose and timing of insulin administration as before switching, but the blood glucose level showed a tendency to decrease within a few days of starting degludec. In the twice-daily group, treatment was initiated at a lower dose insulin degludec (reduced by 10–20%) compared with that of insulin glargine or detemir, but CGM revealed no significant change of the mean blood glucose level.
It is possible that there was a residual effect of insulin glargine or detemir administered immediately before switching to degludec, since insulin glargine has a half-life of approximately 12 h and its duration of action is about 24 h, while insulin detemir has a half-life of about 8–10 h and its duration of action is also about 24 h. It has been reported that the duration of action of these insulins is prolonged in a dose-dependent manner [25
]. However, CGM evaluation was performed 3 days after switching to insulin degludec in the present study and it is unlikely that the effect of glargine or detemir could persist until the third day. There is also a possibility that insulin degludec has a slightly stronger hypoglycemic effect compared with the same dose of glargine or detemir.
Heller et al. [18
] has compared insulin degludec with insulin glargine for 52 weeks and showed that the mean values for TBD and TDD were significantly lower in the insulin degludec group relative to the insulin glargine group. Even in our study, 16 patients with type 1 diabetes mellitus, TBD and TDD were decreased after 12 weeks of treatment.
These results suggest that in patients who have already achieved good glycemic control, with lower fasting glucose levels and hypoglycemia easily, switching to insulin degludec would probably to be initiated at a lower insulin dose than that administered other basal insulin, in order to avoid an increase of hypoglycemia. Even when a patient is on twice daily with other basal insulin, decreasing the dose of insulin degludec is likely to be required. On the other hand, some studies reported that TDD and TBD were similar between insulin degludec and insulin glargine or detemir [20, 21
Previous studies in patients with T1DM who were treated with insulin glargine or detemir showed that the ratio of basal insulin to total daily insulin was about 50–60% [26, 27
]. Another study in diabetic patients who treated with insulin degludec reported that the basal/bolus ratio was about 47:53 [18
]. But several studies reported that the ratio of basal to total daily insulin was about 30–40% in Japanese patients with T1DM who were treated with insulin detemir, glargine or degludec [20, 28, 29
]. The lower daily basal insulin dose in Japanese type 1 diabetes mellitus is probably explained by the generally higher carbohydrate content in Japan [30
]. In this study, in the twice-daily group, the mean basal/bolus ratio was 42/58 before switching and 36/64 after 12 weeks. In the once-daily group, the mean basal/bolus ratio was 38/62 before switching and 35/65 after 12 weeks. These findings do not differ greatly from previous studies in Japan [20, 28, 29, 31
When once-daily injection of insulin glargine or detemir is used as basal insulin in insulin-depleted patients, they often show large diurnal variations of blood glucose due to the dawn phenomenon or Somogyi effect [32
]. In these patients, it was reported that glycemic control can be improved by splitting the basal insulin dose and giving it twice daily [31, 33
]. In the present study, 10 patients have been receiving twice-daily insulin glargine or detemir, so far. The present study demonstrates that changing from twice-daily administration of long-acting insulin to once-daily insulin degludec can maintain the glycemic control with lower number of injection.
The present trial was subject to certain limitations. It was short duration and limited sample size. In addition, the present study was open-label in design and non-cross over trial. Therefore, larger sample size and double-blind crossover comparison may be necessary.