How to transition a patient from Mixtard 30/70 (biphasic insulin aspart 30/70) to a basal-bolus insulin regimen?

Transitioning from Mixtard 30/70 to Basal-Bolus Insulin

Calculate the total daily dose (TDD) from the current Mixtard regimen (34 + 32 = 66 units), then split this as 50% basal insulin (33 units once daily) and 50% rapid-acting prandial insulin (11 units before each of three meals), with immediate titration based on glucose monitoring. 1, 2

Step 1: Calculate Total Daily Dose and Initial Split

Current Mixtard TDD = 66 units/day (34 units morning + 32 units evening)

For the basal-bolus conversion 1, 2:

• Basal insulin (long-acting): 33 units once daily (50% of TDD)
• Prandial insulin (rapid-acting): 33 units total, divided as 11 units before each meal

This 50:50 split between basal and prandial insulin is the standard approach when transitioning from premixed insulin to basal-bolus therapy 1, 2. The American Diabetes Association explicitly recommends this distribution for patients converting from existing insulin regimens 1.

Step 2: Choose Appropriate Insulin Products

Basal insulin options 1:

• Insulin glargine (Lantus/Toujeo): 33 units once daily at the same time each day
• Insulin detemir: May require twice-daily dosing
• Insulin degludec: Once daily with flexible timing

Prandial insulin options 3, 4:

• Rapid-acting analogs (insulin aspart/lispro/glulisine): Inject 5-10 minutes before meals
• Ultra-rapid-acting analogs: Inject 0-2 minutes before meals
• Regular human insulin: Inject 30 minutes before meals (less preferred)

Insulin aspart (NovoLog) should be injected 5-10 minutes before meals into the abdomen, thigh, buttocks, or upper arm, with site rotation within the same region to reduce lipodystrophy risk 3.

Step 3: Implement Aggressive Titration Protocol

Basal insulin titration 1:

• If fasting glucose ≥180 mg/dL: Increase by 4 units every 3 days
• If fasting glucose 140-179 mg/dL: Increase by 2 units every 3 days
• Target fasting glucose: 80-130 mg/dL
• If hypoglycemia occurs: Reduce dose by 10-20% immediately

Prandial insulin titration 1:

• Adjust each meal's dose independently based on 2-hour postprandial glucose
• Increase by 1-2 units or 10-15% every 3 days if postprandial glucose remains elevated
• Target postprandial glucose: <180 mg/dL

Step 4: Critical Monitoring Requirements

Daily glucose monitoring is essential during transition 1:

• Fasting glucose (for basal insulin adjustment)
• Pre-meal glucose (for prandial insulin timing)
• 2-hour postprandial glucose (for prandial insulin dose adjustment)
• Bedtime glucose (to assess overnight basal coverage)

Reassess at every clinical visit for signs of overbasalization 1:

• Bedtime-to-morning glucose differential ≥50 mg/dL
• Basal insulin dose >0.5 units/kg/day
• Recurrent hypoglycemia
• High glucose variability

Step 5: Foundation Therapy Optimization

Continue metformin unless contraindicated, even when intensifying insulin therapy, as it reduces total insulin requirements and provides complementary glucose-lowering effects 1. The dose should be optimized to at least 1000 mg twice daily (2000 mg total) if tolerated 1.

Consider adding a GLP-1 receptor agonist to improve glycemic control while minimizing weight gain and hypoglycemia risk, particularly if the patient is not already on one 1.

Common Pitfalls to Avoid

Do not continue premixed insulin in this patient - randomized trials show that basal-bolus therapy provides better glycemic control with reduced hospital complications compared to premixed insulin regimens, which have significantly increased hypoglycemia rates 5. The Lancet Diabetes and Endocrinology explicitly recommends against premixed insulin in hospital settings due to unacceptably high rates of iatrogenic hypoglycemia 1.

Do not delay prandial insulin addition - when basal insulin exceeds 0.5 units/kg/day (approximately 35-40 units for a 70 kg patient) without achieving targets, adding or intensifying prandial insulin is more appropriate than continuing to escalate basal insulin alone 1.

Do not mix insulin aspart with other insulins except NPH - if mixing is necessary for subcutaneous injection, withdraw insulin aspart into the syringe first and inject immediately 3. However, for optimal control, separate injections are preferred 3.

Rotate injection sites within the same region to prevent lipodystrophy and localized cutaneous amyloidosis, which can distort insulin absorption 3, 4.

Patient Education Essentials

Teach the patient 1:

• Proper insulin injection technique and site rotation
• Recognition and treatment of hypoglycemia (glucose <70 mg/dL)
• Self-monitoring of blood glucose technique
• "Sick day" management rules
• Insulin storage and handling (do not expose to temperatures >98.6°F)
• Timing of rapid-acting insulin relative to meals (5-10 minutes before)

Equip the patient with self-titration algorithms based on self-monitoring of blood glucose to improve glycemic control and reduce therapeutic inertia 1.

Alternative Approach for Lower-Risk Patients

If the patient has well-controlled fasting glucose but elevated postprandial values, consider a stepwise intensification approach 2:

1. Start with optimized basal insulin (33 units once daily)
2. Add single prandial dose (4 units or 10% of basal dose) before the largest meal
3. Progress to two meals, then three meals based on glucose patterns

However, given this patient's total insulin requirement of 66 units daily, immediate basal-bolus therapy is more appropriate than stepwise intensification 1, 2.