U-500 Insulin Dosing Frequency
U-500 regular insulin should be administered two or three times daily due to its distinct pharmacokinetic profile that includes a delayed, blunted peak effect and longer duration of action compared to standard U-100 insulin. 1
Pharmacokinetic Properties of U-500 Insulin
- U-500 regular insulin is five times more concentrated than standard U-100 insulin (500 units/mL vs 100 units/mL), making it appropriate for patients with severe insulin resistance requiring >200 units of insulin daily 2, 3
- Unlike standard U-100 regular insulin, U-500 has characteristics more similar to a premixed intermediate-acting (NPH) and regular insulin product, providing both basal and prandial coverage 1
- U-500 insulin has a delayed onset of action (not effective before 2.5 hours after administration) and significantly longer duration of action than U-100 regular insulin 4
- The duration of action increases with higher doses (longer effect with 200 units compared to 100 units), which may necessitate extended dosing intervals to avoid hypoglycemia 4
Recommended Dosing Regimens
- U-500 insulin can be effectively administered as either twice-daily (BID) or three times daily (TID) injections 1, 5
- Clinical trials have demonstrated that both BID and TID regimens provide significant HbA1c reductions (-1.22% for BID and -1.12% for TID) 5
- The TID regimen showed lower incidence and rate of documented symptomatic hypoglycemia compared to the BID regimen, though severe hypoglycemia rates were similar between both approaches 5
- When converting from high-dose U-100 insulin to U-500, the total daily dose should be maintained but divided into either two or three daily injections 5
Safety Considerations
- Due to its high concentration, U-500 insulin carries an increased risk of dosing errors if not properly prescribed and administered 2, 3
- U-500 insulin is available in both prefilled pens and vials, but should be prescribed with dedicated U-500 syringes when using vials to minimize dosing errors 2
- Careful patient education is essential when initiating U-500 insulin therapy to ensure proper administration and prevent medication errors 6
- Weight gain is a common side effect with U-500 insulin therapy (approximately 5 kg over 24 weeks of treatment) 5
Clinical Application
- For patients requiring U-500 insulin three times daily, the doses should be administered before meals to provide both prandial and basal coverage throughout the day 1, 5
- Due to its delayed onset of action, U-500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal 4
- When initiating U-500 insulin therapy, metformin should generally be continued while other oral agents may be discontinued to avoid unnecessarily complex regimens 1
- U-500 insulin is particularly beneficial for patients with severe insulin resistance who require large doses of insulin, as it reduces injection volume and may improve treatment adherence 1, 3