What is the use of U-500 (concentrated) insulin?

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From the Guidelines

U500 insulin is a highly concentrated form of regular insulin that should be prescribed for patients with severe insulin resistance who require large daily doses of insulin, using dedicated U500 insulin syringes or pens to avoid dosing errors. U500 insulin contains 500 units per milliliter, which is five times more concentrated than standard U100 insulin. It's specifically designed for patients who require large daily doses of insulin (typically more than 200 units per day) 1. The onset of action is 30 minutes to 1 hour, with peak effects at 2-4 hours, and a duration of up to 24 hours. When transitioning from U100 to U500 insulin, the total daily dose is usually kept the same, but divided into two or three injections per day. Close blood glucose monitoring is essential when starting U500 insulin due to its potency. The main advantage of U500 insulin is that it allows delivery of high insulin doses in smaller injection volumes, improving absorption and reducing the number of injections needed. However, due to its concentration, there's an increased risk of severe hypoglycemia if dosing errors occur, so patient education about proper administration is crucial 1.

Some key points to consider when prescribing U500 insulin include:

  • Using dedicated U500 insulin syringes or pens to minimize the risk of dosing errors
  • Close blood glucose monitoring to adjust the dose as needed
  • Patient education on proper administration to avoid severe hypoglycemia
  • U500 insulin has distinct pharmacokinetics with similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin 1
  • U500 insulin can be used as two or three daily injections, making it a convenient option for patients with insulin resistance who require large doses of insulin.

It's also important to note that other concentrated insulins, such as U-300 glargine and U-200 degludec, are available and may be more convenient and comfortable for patients to inject, but U500 insulin is specifically designed for patients with severe insulin resistance who require large daily doses of insulin 1.

From the Research

U500 Insulin Overview

  • U500 insulin is a highly concentrated form of regular insulin, containing 500 units of insulin per milliliter [(2,3)].
  • It is used to treat patients with type 2 diabetes who require high doses of insulin, typically more than 200 units per day [(2,3,4)].

Clinical Use and Efficacy

  • Studies have shown that U500 insulin can be effective in improving glycemic control, with significant reductions in hemoglobin A1c (HbA1c) levels [(5,4)].
  • U500 insulin can be administered as multiple daily injections or via continuous subcutaneous insulin infusion [(2,5)].
  • The use of U500 insulin has been associated with improved patient satisfaction and cost savings 5.

Safety and Potential Side Effects

  • The main limitations of U500 insulin are hypoglycemia and weight gain, as well as the possibility of dosing errors 3.
  • However, studies have not reported severe hypoglycemia associated with the use of U500 insulin [(5,4)].
  • Weight gain has been observed in some studies, but the changes in body weight were not always statistically significant [(5,4)].

Patient Selection and Implementation

  • U500 insulin is indicated for patients with type 2 diabetes who require high doses of insulin and have severe insulin resistance [(2,3,4)].
  • The implementation of U500 insulin therapy requires an experienced physician, a motivated and cooperative patient, and a dynamic diabetes management team 4.
  • A treatment algorithm for converting patients from U100 insulin to U500 insulin has been described, covering dosage requirements ranging from 150 to more than 600 units per day 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

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

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2009

Research

Clinical use of U-500 regular insulin: review and meta-analysis.

Journal of diabetes science and technology, 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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