Maximum Dose of Humulin R U-500
There is no specific maximum dose limit for Humulin R U-500 insulin, but it is indicated for patients requiring more than 200 units of insulin per day, with clinical studies demonstrating safe administration of doses up to 500 units per day divided into multiple injections. 1, 2
Understanding U-500 Insulin
- U-500 regular insulin is five times more concentrated than standard U-100 insulin, containing 500 units/mL versus 100 units/mL 3, 1
- It has a unique pharmacokinetic profile with similar onset to U-100 insulin but a delayed, blunted peak effect and longer duration of action, functioning more like an intermediate-acting insulin that provides both basal and prandial coverage 1, 4
- Humulin R is the only human regular U-500 insulin available on the market 5
Dosing Considerations
- U-500 insulin is specifically indicated for patients with type 2 diabetes who require more than 200 units of insulin per day due to severe insulin resistance 2
- Clinical studies have successfully used U-500 insulin in doses ranging from 242.7 to 343.1 units daily (thrice-daily regimen) and 249.0 to 335.0 units daily (twice-daily regimen) 6
- The duration of action increases when the dose is increased from 100 to 200 units, suggesting that dosing intervals might need to be extended as the dose increases to avoid hypoglycemia 7
Administration Methods
- U-500 insulin can be administered using either a twice-daily (BID) or thrice-daily (TID) regimen 6
- Both regimens have demonstrated significant HbA1c reductions (TID: -1.12%; BID: -1.22%) with comparable increases in total daily dose 6
- U-500 insulin should be administered using dedicated U-500 syringes or the U-500 insulin pen to minimize dosing errors 1
Safety Considerations
- The incidence and rate of documented symptomatic hypoglycemia (≤70 mg/dL) are lower with a thrice-daily regimen compared to twice-daily dosing 6
- U-500 insulin has a delayed onset of action (not before 2.5 hours after administration), making it unsuitable as a premeal bolus insulin to lower glucose two hours after a meal 7
- Weight gain is a common side effect, with clinical studies reporting average weight gains of 4.9-5.4 kg 6
- Due to its concentrated nature, there is an increased risk of dosing errors if not properly prescribed and administered 1
Practical Considerations
- U-500 insulin allows for delivery of larger insulin doses with smaller volumes, leading to better absorption compared to U-100 insulin 5
- It reduces the number of daily injections required for patients on high-dose insulin therapy 6
- The peak concentration and effect are significantly lower for U-500R compared to U-100R at equivalent doses, but the overall insulin exposure and glucose-lowering effect are similar 4
Human Medical Consultant