What is the appropriate dose split for a patient on Mixtard 50/50 (biphasic isophane insulin), with a 2/3 morning and 1/3 evening regimen?

Mixtard 50/50 Dose Split: 2/3 Morning and 1/3 Evening

Yes, the 2/3 morning and 1/3 evening dose split is the appropriate and guideline-recommended regimen for Mixtard 50/50 (biphasic isophane insulin) when initiating or converting to a twice-daily NPH-based insulin regimen. 1

Evidence-Based Dosing Algorithm

Initial Dose Calculation

• When converting from bedtime NPH to twice-daily regimen: Calculate total dose as 80% of current bedtime NPH dose 1
• Distribute as: 2/3 (approximately 67%) given before breakfast, 1/3 (approximately 33%) given before dinner or at bedtime 1

Rationale for This Split

The 2/3 morning and 1/3 evening distribution addresses the physiological insulin requirements throughout the day 1:

• Morning dose (2/3): Covers daytime basal needs and provides prandial coverage for breakfast and lunch 1
• Evening dose (1/3): Provides overnight basal insulin and dinner coverage 1

Titration Strategy

After initiation, titrate based on individualized needs 1:

• Adjust morning dose based on pre-dinner and bedtime glucose readings 1
• Adjust evening dose based on fasting glucose readings 1
• Increase by 2 units every 3 days to reach target fasting plasma glucose (80-130 mg/dL) without hypoglycemia 1
• For hypoglycemia: Determine cause; if no clear reason, reduce the corresponding dose by 10-20% 1

Alternative Dosing Ratios: Research Evidence

While the 2/3:1/3 split is the guideline standard, recent research suggests potential optimization 2:

• A 24-week randomized controlled trial in Korean patients with Type 2 diabetes compared three initial ratios: 50:50,55:45, and 60:40 2
• Key finding: Patients starting with 50:50 required significant dose adjustments to 55:45-60:40 by study end, while those starting with higher morning doses (55:45 or 60:40) maintained stable ratios 2
• This suggests initiating with a slightly higher morning proportion (55:45 to 60:40) may be more appropriate in some populations 2

Critical Pitfalls to Avoid

• Do not delay dose adjustments: Titrate systematically every 3 days based on glucose patterns rather than waiting weeks between changes 1
• Watch for overbasalization: If total insulin dose exceeds 0.5 units/kg/day with persistent hyperglycemia, consider adding separate prandial insulin rather than continuing to escalate the premixed insulin 1
• Recognize limitations of fixed-ratio insulins: Mixtard 50/50 cannot be adjusted separately for basal vs. prandial needs; if this flexibility is required, transition to a self-mixed/split regimen or basal-bolus approach 1

When to Advance Beyond Twice-Daily Premixed Insulin

If A1C remains above target after optimizing twice-daily regimen 1:

• Consider stepwise addition of prandial insulin injections (progressing to three injections daily) 1
• Alternatively, transition to self-mixed/split regimen where NPH and short/rapid-acting insulins can be adjusted separately 1
• Ultimately may proceed to full basal-bolus regimen (basal insulin plus prandial insulin with each meal) 1

Special Considerations for Ramadan Fasting

Research demonstrates that switching evening Mixtard 30/70 to Humalog Mix 50/50 during Ramadan (while maintaining morning Mixtard 30/70) improved postprandial glucose control by 21.1 mg/dL without increasing hypoglycemia 3, 4. This approach provides more rapid-acting insulin for the large evening meal typical during Ramadan 3, 4.