High-dose insulin therapy: is it time for U-500 insulin?

Endocr Pract. 2009 Jan-Feb;15(1):71-9. doi: 10.4158/EP.15.1.71.


Objective: To provide an overview of U-500 regular insulin action, review published clinical studies with U-500 regular insulin, and offer guidance to practicing endocrinologists for identifying patients for whom U-500 regular insulin may be appropriate.

Methods: This review has been produced through a synthesis of relevant published literature compiled via a literature search (MEDLINE search of the English-language literature published between January 1969, and July 2008, related to U-500, insulin resistance, concentrated insulin, high-dose insulin, insulin pharmacokinetics, and diabetes management) and the authors' collective clinical experience.

Results: The obesity epidemic is contributing to an increase in the prevalence of type 2 diabetes, as well as to increasing insulin requirements in insulin-treated patients. Many of these patients exhibit severe insulin resistance, manifested by daily insulin requirements of 200 units or greater or more than 2 units/kg. Delivering an appropriate insulin volume to these patients can be difficult and inconvenient and may be best accomplished with U-500 regular insulin by multiple daily injections or with continuous subcutaneous insulin infusion, rather than with standard U-100 insulin. Implementation of U-500 regular insulin in patients previously on other insulin formulations is described with a treatment algorithm covering dosage requirements ranging from 150 to more than 600 units per day on the basis of the authors' experience.

Conclusions: Regimen conversion of appropriately selected patients from high-dose, U-100 insulin to U-500 regular insulin therapy on the basis of the recommendations presented in this article may potentially result in improved glycemic control and lower cost.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Injections, Subcutaneous
  • Insulin / administration & dosage*
  • Insulin Infusion Systems
  • Treatment Outcome


  • Hypoglycemic Agents
  • Insulin