A patient currently using 250 U of insulin lispro (Humalog) before each meal and 50 U of insulin glargine (Lantus) daily—what should her U‑500 regular insulin dosing regimen be?

Converting from High-Dose Humalog + Lantus to U-500 Regular Insulin

For a patient taking 250 units of Humalog three times daily (750 units total) plus 50 units of Lantus (total daily dose = 800 units), convert to U-500 regular insulin by calculating 80% of the total daily dose (640 units), then administering it as 320 units twice daily before breakfast and dinner.

Immediate Conversion Protocol

Step 1: Calculate Total Daily Dose

• Current regimen: 250 U Humalog × 3 meals = 750 U + 50 U Lantus = 800 units total daily dose 1
• This represents approximately 1.0 units/kg/day for an average adult, which is typical for insulin-resistant type 2 diabetes 1

Step 2: Apply U-500 Conversion Factor

• Reduce the total daily dose by 20% when converting from multiple daily injections to U-500 regular insulin to account for improved insulin absorption and reduced injection site variability 1
• 800 units × 0.80 = 640 units of U-500 regular insulin per day 1

Step 3: Divide into Twice-Daily Dosing

• U-500 regular insulin should be administered twice daily, typically before breakfast and dinner 2, 3
• Split the 640 units as 320 units before breakfast and 320 units before dinner 2, 3
• Administer 30 minutes before meals (not 0-15 minutes like rapid-acting analogs) because U-500 regular insulin has a slower onset 1, 4

Critical Timing and Administration Details

Injection Timing

• Give U-500 regular insulin 30 minutes before breakfast and 30 minutes before dinner 4
• This timing is essential because regular insulin has an onset of 30-60 minutes, unlike the 0-15 minute onset of lispro 1, 4

Pharmacokinetic Considerations

• U-500 regular insulin has a duration of action of 18-24 hours when given in high doses, providing both prandial and basal coverage 1
• Peak action occurs at 4-8 hours after injection, covering both the immediate meal and providing basal insulin between doses 1
• The twice-daily regimen eliminates the need for separate basal insulin (Lantus) 2, 3

Titration Protocol

Initial Monitoring

• Check fasting blood glucose daily and pre-dinner glucose to guide dose adjustments 1
• Monitor for hypoglycemia 4-8 hours after each injection when U-500 regular insulin peaks 1

Dose Adjustment Algorithm

• If fasting glucose is 140-179 mg/dL, increase the dinner dose by 10 units (approximately 3% increase) every 3 days 1
• If fasting glucose is ≥180 mg/dL, increase the dinner dose by 20 units (approximately 6% increase) every 3 days 1
• If pre-dinner glucose is elevated, increase the breakfast dose by 10-20 units every 3 days using the same thresholds 1
• Target fasting and pre-dinner glucose 80-130 mg/dL 1

Hypoglycemia Management

• If hypoglycemia occurs, reduce the corresponding dose by 10-20% immediately 1
• The most common time for hypoglycemia is 4-8 hours post-injection during peak insulin action 1

Critical Safety Considerations

U-500 Concentration Awareness

• U-500 insulin contains 500 units per mL (5 times more concentrated than U-100 insulin) 1
• Dosing errors are catastrophic—always use U-500 specific syringes or pens to prevent 5-fold overdosing 1
• Never use standard U-100 syringes with U-500 insulin 1

Metformin Continuation

• Continue metformin at maximum tolerated dose (up to 2000-2550 mg daily) unless contraindicated, as this combination reduces total insulin requirements and provides superior glycemic control 1

Monitoring Frequency

• Check glucose before breakfast, before dinner, and at bedtime during the first 2-4 weeks 1
• Once stable, continue fasting and pre-dinner monitoring at minimum 1

Common Pitfalls to Avoid

Timing Errors

• Do not give U-500 regular insulin 0-15 minutes before meals like rapid-acting analogs—this will cause post-meal hyperglycemia and delayed hypoglycemia 1, 4
• The 30-minute pre-meal timing is non-negotiable for optimal postprandial control 4

Dosing Errors

• Never attempt to split U-500 into three daily doses mimicking the previous Humalog regimen—the prolonged duration of U-500 makes twice-daily dosing optimal 2, 3
• Do not continue Lantus when starting U-500 regular insulin, as the basal coverage is already provided by the U-500 2, 3

Under-Dosing Risk

• The 20% dose reduction (from 800 to 640 units) is conservative and evidence-based 1
• If glucose remains elevated after 2 weeks, do not hesitate to increase doses by 10-20 units every 3 days 1
• When total U-500 dose exceeds 0.5 units/kg/day without achieving targets, consider adding a GLP-1 receptor agonist rather than continuing dose escalation 1

Hypoglycemia Prevention

• The overlapping action of morning and evening U-500 doses creates continuous insulin coverage 1
• Patients must maintain consistent meal timing and carbohydrate intake to match the insulin action profile 2
• Skipping meals with U-500 on board carries severe hypoglycemia risk due to the prolonged duration of action 1

Expected Outcomes

• With appropriate U-500 dosing, expect HbA1c reduction of 1-2% over 3-6 months 1
• The simplified twice-daily regimen improves adherence compared to multiple daily injections 2, 3
• Total injection volume decreases from 8 mL daily (800 units of U-100) to 1.28 mL daily (640 units of U-500), reducing injection site complications 1