SAN FRANCISCO — For patients who need large doses of insulin (more than 200 U/day), U-500 insulin is the best choice because of more predictable pharmacokinetics and lower cost per unit.
“[With] a huge volume of insulin—60 or 80 U—you're going to have more variability in the absorption” with conventional insulins such as U-100, lispro, or glargine, Dr. Irl B. Hirsch told a meeting sponsored by the American Diabetes Association.
Although U-500 insulin is called “regular” insulin, “it ain't like regular insulin” because it's five times more concentrated and has longer pharmacokinetics, said Dr. Hirsch, professor of medicine at the University of Washington, Seattle. This has caused confusion in some hospitals regarding dosing.
For clarity, some physicians refer to milliliter or cubic centimeter measurements when referring to U-500 insulin, but “there's no formal consensus on this,” he said.
Twenty U of U-500 insulin in a U-100 syringe is 0.2 mL—the same dose as 100 U of U-100 insulin in a volume of 1 mL. U-500 insulin is available only from Eli Lilly & Co., for which Dr. Hirsch is a consultant.
The duration of action of U-500 insulin is up to 24 hours. Large doses of insulin can be given with one-fifth the volume using U-500 insulin, so there's less day-to-day variation in absorption and less variability of absorption in different body regions.
U-500 insulin can be helpful especially in those needing large depots of insulin but who have little subcutaneous tissue. A smaller volume of insulin is less painful for these patients.
The pharmacokinetic and pharmacodynamic characteristics of huge doses of either conventional or NPH insulin per injection have not been well studied since not many patients need such high doses, Dr. Hirsch noted.
With U-500 insulin, “Don't think about this as giving prandial insulin. The basal/prandial distinction we make with insulin components for a typical basal bolus sort of goes away when we're talking about U-500 insulin, since it is really both.”
The National Institutes of Health published an algorithm suggesting that insulin-resistant patients who need less than 200 U/day use U-100 insulin, and that U-500 insulin be considered for severely insulin-resistant patients who need more (Diabetes Care 2005;28:1240–4).
A twice-a-day regimen of U-500 insulin would be used for patients who need 200–300 U/day, and a three-times-a-day regimen would apply to patients who need 300–750 U/day. For 750–2,000 U/day, patients would use U-500 insulin t.i.d. plus a fourth dose at bedtime. Above 2,000 U/day, an insulin pump is best, Dr. Hirsch said.
Although a 20-mL vial of U-500 insulin costs about $260, compared with $43-$89 for a 10-mL vial of U-100 insulin, lispro, or aspart, the cost per unit is cheapest with U-500—3 cents a unit rather than 4 to 9 cents “This is the economical way,” he said.
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