How long before a meal should U500 (regular insulin) be administered?

U-500 Insulin Timing Before Meals

U-500 regular insulin should NOT be taken immediately before meals as a prandial bolus insulin; instead, it should be administered 30 minutes or more before eating, or dosed as a twice-daily or three-times-daily regimen independent of meal timing, due to its delayed onset of action that does not begin until at least 2.5 hours after injection. 1

Critical Pharmacokinetic Properties

U-500 regular insulin has fundamentally different pharmacokinetics compared to standard U-100 regular insulin that directly impact meal timing:

• Delayed onset of action: Research demonstrates that U-500 insulin has no onset of action before 2.5 hours after administration, regardless of whether 100 or 200 units are given 1
• Prolonged duration: U-500 functions more like an intermediate-acting (NPH) insulin with both basal and prandial properties, rather than as a typical prandial insulin 2, 3
• Dose-dependent duration: The duration of action increases significantly when the dose is increased from 100 to 200 units 1

Recommended Dosing Strategy

Given these unique pharmacokinetic properties, U-500 insulin should be used differently than standard prandial insulins:

• Twice-daily or three-times-daily dosing: U-500 is typically administered as 2-3 daily injections (commonly 100 units twice daily before breakfast and dinner) rather than as a traditional premeal bolus 3, 4
• Not for postprandial control: U-500 should not be used as a premeal bolus insulin to lower glucose 2 hours after a meal, as its onset is too delayed 1
• Extended dosing intervals: Dosing intervals may need to be extended as the dose increases to avoid hypoglycemia, given the prolonged duration of action 1

Contrast with Standard Prandial Insulins

For context, standard rapid-acting insulin analogues (like lispro or aspart) should be taken 15-20 minutes before meals for optimal postprandial glucose control 5, while regular U-100 insulin is typically taken 15-30 minutes before eating 2. U-500 insulin does not follow these timing principles due to its fundamentally different pharmacokinetic profile.

Critical Safety Considerations

• Dosing errors: Always use dedicated U-500 syringes or pens to minimize potentially fatal dosing errors 3
• Hypoglycemia risk: The prolonged duration of action requires careful attention to dosing intervals and meal timing to prevent delayed hypoglycemia 1, 4
• Patient education: Ensure patients understand that U-500 does not act like U-100 regular insulin and requires different timing strategies 3

Clinical Application

For patients requiring more than 200 units of insulin daily, U-500 provides convenient twice-daily or three-times-daily dosing as monotherapy, eliminating the need for separate basal and bolus insulins 3, 4. The typical starting regimen is 100 units twice daily before breakfast and dinner, with subsequent titration based on self-monitoring blood glucose patterns 3.