Insulin degludec, the longest and flattest basal insulin
Insulin degludec is a basal insulin (a slow, steady background insulin that holds blood glucose stable between meals) with the longest and flattest action, lasting up to about 42 hours.
Remember
Of the long-acting basal insulins, degludec works for the longest time, up to about 42 hours, and its action is the flattest, with no obvious surge of effect. Glargine and detemir, other long-acting basal insulins, last about 24 hours and about 16 to 20 hours respectively.
Memory aid
a tap left dripping through the day
Picture basal insulin as a tap left dripping through the day, and compare how steady and how long each insulin drips.
Insulin degludec is an ultra-long-acting basal insulin: it gives slow, steady background cover and keeps working for far longer than one day. Bolus insulin is the kind taken with food to cover meals. In a basal-bolus regimen, a long-acting basal insulin is usually given once daily and rapid-acting insulin is added at meals.
After injection, degludec assembles into multi-hexamers, long chains made from hexamers (each hexamer is a cluster of six insulin molecules), and these release insulin slowly and continuously. Its time-action profile, meaning how strongly the insulin works at each hour after injection, is therefore very flat, or peakless. A peak is the time of strongest insulin action, when blood glucose is most likely to fall too low.
A basal insulin with a peak makes nocturnal hypoglycaemia, meaning low blood glucose during the night, more likely. This is the weakness of intermediate-acting insulin such as NPH (neutral protamine Hagedorn, or isophane) insulin, which peaks at about 4 to 8 hours and lasts 12 to 18 hours, so it is often given twice daily.
Degludec acts for up to about 42 hours. Glargine, which gives fairly flat once-daily cover, lasts about 24 hours, and detemir, also a long-acting basal insulin, lasts 16 to 20 hours, so degludec acts for longer than either and has the flattest profile of the long-acting insulins. Because a dose lasts well beyond the 24-hour dosing interval, it overlaps with the next dose, and the timing of each injection is less rigid.
Key facts
- Duration
- glargine acts for about 24 hours, detemir for about 16 to 20 hours and degludec for up to about 42 hours.
- Half-life
- the terminal half-life of degludec, the time for the blood level to fall by half, is about 25 hours, roughly double that of glargine.
- Variability
- in studies, degludec had lower day-to-day variability than glargine, variability being the swings in blood glucose.
- Timing
- because the action is so long, the exact time of each injection is less rigid; in flexible-dosing trials, injections at varying times were acceptable provided at least 8 hours separated doses.
- Caution
- a smoother profile may reduce the risk of nocturnal hypoglycaemia, but the benefit seen in trials is modest.
Exam traps
- Glargine is a familiar basal insulin that gives fairly flat once-daily cover, but acting for about 24 hours it does not give the longest cover, because degludec lasts considerably longer.
- Detemir is also a long-acting basal insulin, but its action lasts only about 16 to 20 hours, so it gives less of the very long, flat cover that degludec gives.
- NPH insulin is a traditional basal insulin, but its peak at about 4 to 8 hours and its duration of 12 to 18 hours make it neither the longest nor the flattest option.
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