Insulin detemir—In this insulin the terminal threonine is dropped from the B30 position and myristic acid (a C-14 fatty acid chain) is attached to the B29 lysine. These modifications prolong the availability of the injected analog by increasing both self-aggregation in subcutaneous tissue and reversible albumin binding. The affinity of insulin detemir is fourto fivefold lower than that of human soluble insulin and, therefore, the U100 formulation of insulin detemir has a concentration of 2400 nmol/mL compared with 600 nmol/mL for NPH. The duration of action for insulin detemir is about 17 hours at therapeutically relevant doses. It is recommended that the insulin be injected once or twice a day to achieve a stable basal coverage. This insulin has been reported to have lower within-subject pharmacodynamic variability compared with NPH insulin and insulin glargine.
4.
Insulin Degludec—In this insulin analog, the threonine at position B30 has been removed and the lysine at position B29 is conjugated to hexadecanoic acid via a gamma-l-glutamyl spacer. In the vial, in the presence of phenol and zinc, the insulin is in the form of dihexamers but, when injected subcutaneously, it self-associates into large multihexameric chains consisting of thousands of dihexamers. The chains slowly dissolve in the subcutaneous tissue, and insulin monomers are steadily released into the systemic circulation. The half-life of the insulin is 25 hours. Its onset of action is in 30–90 minutes, and its duration of action is more than 42 hours. It is recommended that the insulin be
FIGURE 41–5 Extent and duration of action of various types of insulin as indicated by the glucose infusion rates (mg/kg/min) required to maintain a constant glucose concentration. The durations of action shown are typical of an average dose of 0.2–0.3 U/kg. The durations of regular and NPH insulin increase considerably when dosage is increased.
injected once or twice a day to achieve a stable basal coverage. Insulin degludec is available in two concentrations, U100 and U200, and dispensed in pre-filled disposable pens.
5. Mixtures of insulins—Because intermediate-acting NPH insulins require several hours to reach adequate therapeutic levels, their use in patients with diabetes usually requires supplements of rapidor short-acting insulin before meals. For convenience, these are often mixed together in the same syringe before injection. The regular insulin or rapidly acting insulin analog is withdrawn first, then the NPH insulin and then injected immediately.