In a recent report in Diabetes Care, experience using U-500 regular insulin (U-500) in syndromic forms of insulin resistance was described (1). Due to its higher concentration, U-500 has pharmacokinetics that are believed to be similar to U-100 NPH insulin peaking later and lasting longer than U-100 regular insulin. These authors suggest that U-500 may be used in type 2 diabetic patients with severe insulin resistance who fail usual treatment (1). We report our experience using U-500 insulin in type 2 diabetic patients with poor glycemic control despite >200 units of insulin/day.

We studied 15 patients (7 men and 8 women, mean age 59.8 years, mean weight 126.6 kg) using a mean daily dose of insulin U-100 of 219 units and mean HbA1c (A1C) of 9.8%. After initiation of U-500, the A1C decreased to 7.9% at 3 months and to 7.6% at 1 year. The patients required a mean of 285 units of U-500 at 3 months and 335 units at 1 year (this corresponds to the 57 and 67 markings on a U-100 syringe, respectively). Their weight increased by 3.2% at 3 months and by 1.6% at 12 months. At baseline, hypoglycemia rarely occurred (one to two episodes per month). The frequency of hypoglycemia did not change at 3 and 12 months after the initiation of U-500, and none of these episodes were severe. With the exception of insulin U-500, no other changes were made in the antidiabetes medications.

Reports on the use of U-500 in type 2 diabetic patients have been limited to several case reports and case series (24). The largest series examined 20 poorly controlled diabetic patients with severe insulin resistance, and a 1% reduction in A1C was observed after 6 months of administration of U-500 (4). In our series, reduction in A1C was more pronounced.

Our experience adds to the evidence from others that U-500 can be used effectively in a subset of type 2 diabetic patients with poor glycemic control despite >200 units of insulin daily (14). An ∼2% reduction in A1C, small weight gain, and no increase in hypoglycemia were observed. This improvement in glycemic control could be related to delivery of higher doses of insulin, better absorption, and/or differences in duration of action. Large, prospective studies are needed to confirm these findings. Pharmacodynamic and pharmacokinetic studies of U-500 would be helpful to better understand optimal U-500 dosing regimens in this difficult-to-control subgroup of patients.

Cochran E, Musso C, Gorden P: The use of U-500 in patients with extreme insulin resistance.
Diabetes Care
Fain JA: Insulin resistance and the use of U-500 insulin: a case report.
Diabetes Educ
Knee T, Seidensticker D, Walton J, Solberg L, Lasseter D: A novel use of U-500 insulin for continuous subcutaneous insulin infusion in patients with insulin resistance: a case series.
Endocr Pract
Neal J: Analysis of effectiveness of human U-500 insulin in patients unresponsive to conventional insulin therapy.
Endocr Pract