Safety and Effectiveness of U-500 Insulin Therapy in Patients with Insulin-Resistant Type 2 Diabetes Mellitus

Study Objective. To assess the safety and effectiveness of highly concentrated U-500 regular insulin in patients with insulin-resistant type 2 diabetes mellitus who were switched from U-100 insulin. Design. Retrospective cohort study Setting. Outpatient diabetes management clinic. Patients. Twenty-one adults with poorly controlled type 2 diabetes and insulin resistance who were referred to the clinic between July 1, 2007, and June 30, 2008, and whose therapy was changed from large doses of U-100 insulin to U-500 insulin. Measurements and Main Results. Demographic and clinical data were collected through a computerized medical record system. Insulin resistance was defined as a requirement of more than 200 units/day of insulin and more than 100 units/injection. The primary outcome was the change in hemoglobin A(1C) (A1C) after switching from any type of U-100 insulin to stabilization with U-500 highly concentrated regular insulin. Secondary outcomes were the changes in number of daily insulin injections, daily insulin dose, and body weight. With use of U-500 insulin, patients were able to achieve an average reduction in A1C of 1.7% (p<0.001). The mean number of daily injections decreased from 4.3 with U-100 insulin to 2.7 after using U-500 insulin (p<0.001), but changes in body weight after the change in insulin were not statistically significant (279.8 vs 279.2 lbs, p=0.429). No patient discontinued U-500 insulin during the study, and none experienced hypoglycemia severe enough to require the assistance of another individual. Conclusion. In patients with insulin-resistant diabetes who have requirements of more than 200 units/day or 100 units/injection, use of U-500 regular insulin provided the same or better glucose control compared with U-100 insulin, with fewer daily injections and reduced injection volume. Although this drug represents an excellent treatment option, its safe use requires an experienced physician, a motivated and cooperative patient, and a dynamic diabetes management team.