While insulin aspart has been approved for intravenous use (eg, in hyperglycemic emergencies), there is no advantage in using insulin aspart over regular insulin by this route. A U200 concentration of insulin lispro is available in a disposable prefilled pen. The only advantage of the U200 over the U100 insulin lispro preparation is that it delivers the same dose in half the volume.
B. Long-Acting Insulin Preparations (Tables 41–5, 41–6) 1.
NPH (neutral protamine Hagedorn, or isophane) insulin—NPH insulin is an intermediate-acting insulin whose absorption and onset of action are delayed by combining appropriate amounts of insulin and protamine so that neither is present in an uncomplexed form (“isophane”). After subcutaneous injection, proteolytic tissue enzymes degrade the protamine to permit absorption of insulin. NPH insulin has an onset of approximately 2–5 hours and duration of 4–12 hours (Figure 41–5); it is usually mixed with regular, lispro, aspart, or glulisine insulin and given two to four times daily for insulin replacement. The dose regulates the action profile; specifically, small doses have lower, earlier peaks and a short duration of action with the converse true for large doses.
2.
Insulin glargine—Insulin glargine is a soluble, “peakless” (ie, having a broad plasma concentration plateau), long-acting insulin analog. The attachment of two arginine molecules to the B-chain carboxyl terminal and substitution of a glycine for asparagine at the A21 position created an analog that is soluble in an acidic solution but precipitates in the more neutral body pH after subcutaneous injection. Individual insulin molecules slowly dissolve away from the crystalline depot and provide a low, continuous level of circulating insulin. Insulin glargine has a slow onset of action (1–1.5 hours) and achieves a maximum effect after 4–6 hours. This maximum activity is maintained for 11–24 hours or longer. Glargine is usually given once daily, although some very insulin-sensitive or insulin-resistant individuals benefit from split (twice a day) dosing. To maintain solubility, the formulation is unusually acidic (pH 4.0), and insulin glargine should not be mixed with other insulins. Separate syringes must be used to minimize the risk of contamination and subsequent loss of efficacy. The absorption pattern of insulin glargine appears to be independent of the anatomic site of injection, and this drug is associated 1 2 3 4 5 6 7 8 9101112131415161718192021222324 Time (h) Insulin lispro, aspart, glulisine with less immunogenicity than human insulin in animal studies. Glargine’s interaction with the insulin receptor is similar to that of native insulin and shows no increase in mitogenic activity in vitro. It has sixfold to sevenfold greater binding than native insulin to the insulin-like growth factor 1 (IGF-1) receptor, but the clinical significance of this is unclear.
3.