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For Large Doses of Insulin, Consider U-500

I often start patients on insulin pumps and because of their large use of insulin start them on U-500 Regular insulin made by Eli Lilly. Lately I have started converting syringe patients over to this strength of insulin also. Now there seems to be an increased interest in this insulin and Dr. Irl B. Hirsch, Professor of Medicine, University Washington Seattle has written a great feature For Large Doses of Insulin, Consider U-500 and we have it for you

For Large Doses of Insulin, Consider U-500

SAN FRANCISCO — For patients who need large doses of insulin (more than 200 U/day), U-500 insulin is the best choice among insulins because of more predictable pharmacokinetics and lower cost per unit, according to Dr. Irl B. Hirsch.

“When we give 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, glargine, or lispro, he said at 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 clinicians have started referring to milliliter or cubic centimeter measurements when talking about U-500 insulin, “though there’s no formal consensus on this,” he said. Twenty U of U-500 insulin in a U-100 syringe is 0.2 mL, which is the same dose as 100 U of U-100 insulin in a volume of 1 mL.

“You can see why there’s so much confusion,” he said. 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, “a little closer to NPH insulin than to regular insulin—somewhere in between,” he said. Because large doses of insulin can be given with one-fifth the volume using U-500 insulin, 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 for patients who need large depots of insulin but have little subcutaneous tissue. Giving a smaller volume of insulin is less painful for these patients.

Dr. Hirsch described a 32-year-old woman with congenital lipodystrophy who had very little fat tissue. She was referred for diabetes control after being hospitalized for hypertriglyceridemia and pancreatitis for the third time in a year. This patient was taking 60 U of glargine b.i.d. and 60–80 U of lispro before meals, plus rosiglitazone. She weighed around 65 kg. Her hemoglobin A1c level was 12%, and her glucose meter readings showed an average glucose level of 275 mg/dL, with a standard deviation of 85 mg/dL.

“She wasn’t trying to fool anybody. She was very frustrated with these very high numbers,” and U-500 helped her stabilize, he said.

The pharmacokinetic-pharmacodynamic characteristics of huge doses of either conventional or NPH insulin per injection have not been well studied. “These are not real common patients” who 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,” he added.

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.

This is article came from SHERRY BOSCHERT (San Francisco Bureau)