Safety and effectiveness of U-500 insulin therapy in patients with insulin-resistant type 2 diabetes mellitus

Pharmacotherapy. 2011 Jul;31(7):695-702. doi: 10.1592/phco.31.7.695.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / drug effects
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / therapeutic use*
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Retrospective Studies


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin